Cancer

Med Hypotheses. 2007;68(3):562-4. Epub 2006 Oct 11.
Heme of consumed red meat can act as a catalyst of oxidative damage
and could initiate colon, breast and prostate cancers, heart disease
and other diseases.
Tappel A.
Department of Food Science and Technology, University of California,
Davis, CA 95616, USA. altappel@ucdavis.edu

    Dietary epidemiological studies indicate correlations between the
consumption of red meat and/or processed meat and cancer of the colon,
rectum, stomach, pancreas, bladder, endometrium and ovaries, prostate,
breast and lung, heart disease, rheumatoid arthritis, type 2 diabetes
and Alzheimer's disease. The correlation of all these major diseases
with dietary red meat indicates the presence of factors in red meat
that damage biological components. This hypothesis will focus on the
biochemistry of heme compounds and their oxidative processes.

    Raw red meat contains high levels of oxymyoglobin and deoxymyoglobin and
oxyhemoglobin and deoxyhemoglobin and cytochromes in muscle and other
tissues. Cooked and processed meat contain hemichromes and
hemochromes. After being eaten heme proteins are hydrolyzed to amino
acids and peptides and the heme group which is coordinated with strong
ligands. The iron of heme coordinates to the sulfur, nitrogen or
oxygen of amino acids and peptides and other biological components.
The coordinated heme groups are absorbed and transported by the blood
to every organ and tissue. Free and coordinated heme preferentially
catalyze oxidative reactions. Heme catalyzed oxidations can damage
lipids, proteins, DNA and other nucleic acids and various components
of biological systems. Heme catalysis with hydroperoxide intermediates
can initiate further oxidations some of which would result in
oxidative chain reactions. Biochemical and tissue free radical damage
caused by heme catalyzed oxidations is similar to that resulting from
ionizing radiation. Oxidative biochemical damage is widespread in
diseases. It is apparent that decreasing the amount of dietary red
meat will limit the level of oxidative catalysts in the tissues of the
body. Increasing consumption of vegetables and fruits elevates the
levels of antioxidative components, for example, selenium, vitamin E,
vitamin C, lycopene, cysteine-glutathione and various phytochemicals.
These detrimental processes of heme catalysis of oxidative damage
hypothesized here are not well recognized. More investigative studies
in this field need to be done.

  Meat consumption, particularly of red and processed meat, is one of the most thoroughly studied dietary factors in relation to colon cancer. However, it is not clear whether meat, red meat, heterocyclic amines (HCA), or polycyclic aromatic hydrocarbons (PAH) are associated with the risk for rectal cancer. Rectal cancer cases (n = 952) and controls (n = 1205) from Utah and Northern California were recruited from a population-based case-control study between September 1997 and February 2002. Detailed in-person interviews regarding lifestyle, medical history, and diet were conducted. DNA was extracted from peripheral lymphocytes obtained from whole-blood samples, and glutathione S-transferase (GST)M1 enzyme and N-acetyl transferase (NAT)2 enzyme genotypes were assessed. Although energy and cholesterol intakes were higher among cases than controls, adjustment for confounders accounted for the differences. Increased consumption of well-done red meat [odds ratio (OR) 1.33 95% CI 0.98, 1.79] was associated with an (P = 0.04) increase in risk for rectal cancer among men. The mutagen index, calculated on the bases of reported amount, doneness, and method of cooking meat, was also positively but not significantly (P = 0.24) associated with risk of rectal cancer for men (OR 1.37 95% CI 0.98, 1.92). NAT2-imputed phenotype and GSTM1 did not consistently modify rectal cancer risk associated with meat intake. These data suggest that mutagens such as HCA that form when meat is cooked may be culpable substances in rectal cancer risk, not red meat itself.

PMID: 15051825

  BACKGROUND: Associations between colon and rectal cancer and intakes of vegetables, other plant foods, and fiber have stimulated much debate.
  OBJECTIVE: We examined the association between rectal cancer and plant food and fiber intakes.
  DESIGN: Data from 952 incident cases of rectal cancer were compared with data from 1205 population-based controls living in Utah or enrolled in the Kaiser Permanente Medical Care Program in northern California
  RESULTS: Rectal cancer was inversely associated with intakes of vegetables (odds ratio: 0.72; 95% CI: 0.54, 0.98), fruit (0.73; 0.53, 0.99), and whole-grain products (0.69; 0.51, 0.94), whereas a high intake of refined-grain products was directly associated with an increased risk of rectal cancer (1.42; 1.04, 1.92). Similarly, relative to low fiber intakes, high intakes of dietary fiber reduced the risk of rectal cancer (0.54; 0.37, 0.78). The reduced risk of rectal cancer associated with vegetable (0.48; 0.29, 0.80), fruit (0.63; 0.38, 1.06), and fiber (0.40; 0.22, 0.71) intakes was strongest for persons who received the diagnosis after age 65 y. A threshold effect at approximately 5 servings of vegetables/d was needed to see a reduced risk of rectal cancer.
  CONCLUSIONS: The results suggest that plant foods may be important in the etiology of rectal cancer in both men and women. Age at diagnosis appears to play an important role in the association.

PMID: 14749234

  BACKGROUND: Epidemiologic studies found that high tomato intakes reduce the risk of colorectal cancers. This beneficial effect is assumed to be caused by high intakes of lycopene, a carotenoid with strong antioxidant activity that is present predominantly in tomatoes.
  OBJECTIVE: We assessed the relation between plasma lycopene concentrations and colorectal adenomas, the precursors for most colorectal cancers. In addition, the concentrations of 2 other antioxidants, beta-carotene and alpha-tocopherol, were measured. DESIGN: White subjects undergoing a complete colonoscopy were included in the study (73 with adenomas, 63 without any polyps, and 29 with hyperplastic polyps). A detailed dietary history and information on alcohol consumption and smoking habits were collected from all subjects. Plasma lycopene, beta-carotene, and alpha-tocopherol concentrations were measured by using HPLC.
  RESULTS: Patients with adenomas and control subjects without polyps did not differ significantly in body mass index; intakes of energy, fat, protein, carbohydrates, fiber, beta-carotene, and alcohol; or prevalence of smoking, but patients with adenomas were slightly older. The median plasma lycopene concentration was significantly lower in the adenoma group than in the control group (-35%; P = 0.016). The median plasma beta-carotene concentration also tended to be lower in the adenoma group (-25.5%), but the difference was not significant. In the multiple logistic regression, only smoking (odds ratio: 3.02; 95% CI: 1.46, 6.25; P = 0.003) and a plasma lycopene concentration < 70 microg/L (odds ratio: 2.31; 1.12, 4.77; P = 0.023) were risk factors for adenomatous polyps. Patients with hyperplastic polyps did not differ significantly from control subjects in any variable.
  CONCLUSION: Our findings support the hypothesis that lycopene contributes to the protective effect of high tomato intakes against the risk of colorectal adenomas.

PMID: 14668286

  BACKGROUND: International comparisons and case-control studies have suggested a positive relation between dietary fat intake and breast cancer risk, but prospective studies, most of them involving postmenopausal women, have not supported this association. We conducted a prospective analysis of the relation between dietary fat intake and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II.
  METHODS: Dietary fat intake and breast cancer risk were assessed among 90 655 premenopausal women aged 26 to 46 years in 1991. Fat intake was assessed with a food-frequency questionnaire at baseline in 1991 and again in 1995. Breast cancers were self-reported and confirmed by review of pathology reports. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided.
  RESULTS: During 8 years of follow-up, 714 women developed incident invasive breast cancer. Relative to women in the lowest quintile of fat intake, women in the highest quintile of intake had a slight increased risk of breast cancer (RR = 1.25, 95% CI = 0.98 to 1.59; P(trend) =.06). The increase was associated with intake of animal fat but not vegetable fat; RRs for the increasing quintiles of animal fat intake were 1.00 (referent), 1.28, 1.37, 1.54, and 1.33 (95% CI = 1.02 to 1.73; P(trend) =.002). Intakes of both saturated and monounsaturated fat were related to modestly elevated breast cancer risk. Among food groups contributing to animal fat, red meat and high-fat dairy foods were each associated with an increased risk of breast cancer.
  CONCLUSIONS: Intake of animal fat, mainly from red meat and high-fat dairy foods, during premenopausal years is associated with an increased risk of breast cancer.

PMID: 12865454

  It is the position of the American Dietetic Association and Dietitians of Canada that appropriately planned vegetarian diets are healthful, nutritionally adequate, and provide health benefits in the prevention and treatment of certain diseases. Approximately 2.5% of adults in the United States and 4% of adults in Canada follow vegetarian diets. A vegetarian diet is defined as one that does not include meat, fish, or fowl. Interest in vegetarianism appears to be increasing, with many restaurants and college foodservices offering vegetarian meals routinely. Substantial growth in sales of foods attractive to vegetarians has occurred and these foods appear in many supermarkets. This position paper reviews the current scientific data related to key nutrients for vegetarians including protein, iron, zinc, calcium, vitamin D, riboflavin, vitamin B-12, vitamin A, n-3 fatty acids, and iodine. A vegetarian, including vegan, diet can meet current recommendations for all of these nutrients. In some cases, use of fortified foods or supplements can be helpful in meeting recommendations for individual nutrients. Well-planned vegan and other types of vegetarian diets are appropriate for all stages of the life-cycle including during pregnancy, lactation, infancy, childhood, and adolescence. Vegetarian diets offer a number of nutritional benefits including lower levels of saturated fat, cholesterol, and animal protein as well as higher levels of carbohydrates, fibre, magnesium, potassium, folate, antioxidants such as vitamins C and E, and phytochemicals. Vegetarians have been reported to have lower body mass indices than non-vegetarians, as well as lower rates of death from ischemic heart disease, lower blood cholesterol levels, lower blood pressure, and lower rates of hypertension, type 2 diabetes, and prostate and colon cancer. While a number of federally funded and institutional feeding programs can accommodate vegetarians, few have foods suitable for vegans at this time. Because of the variability of dietary practices among vegetarians, individual assessment of dietary intakes of vegetarians is required. Dietetics professionals have a responsibility to support and encourage those who express an interest in consuming a vegetarian diet. They can play key roles in educating vegetarian clients about food sources of specific nutrients, food purchase and preparation, and any dietary modifications that may be necessary to meet individual needs. Menu planning for vegetarians can be simplified by use of a food guide that specifies food groups and serving sizes.

PMID: 12826028

  Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.

PMID: 12730430

  Background: Although dietary fibre has been reported to have no association with colorectal adenoma and cancer, in some studies this topic remains controversial. Methods We used a 137-item food frequency questionnaire to assess the relation of fibre intake and frequency of colorectal adenoma. The study was done within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomised controlled trial designed to investigate methods for early detection of cancer. In our analysis, we compared fibre intake of 33,971 participants who were sigmoidoscopy-negative for polyps, with 3591 cases with at least one histologically verified adenoma in the distal large bowel (ie, descending colon, sigmoid colon, or rectum). Odds ratios were estimated by logistic regression analysis.
  Findings: High intakes of dietary fibre were associated with a lower risk of colorectal adenoma, after adjustment for potential dietary and non-dietary risk factors. Participants in the highest quintile of dietary fibre intake had a 27% (95% CI 14-38, ptrend=0.002) lower risk of adenoma than those in the lowest quintile. The inverse association was strongest for fibre from grains and cereals and from fruits. Risks were similar for advanced and non-advanced adenoma. Risk of rectal adenoma was not significantly associated with fibre intake.
  Interpretation: Dietary fibre, particularly from grains, cereals, and fruits, was associated with decreased risk of distal colon adenoma.

PMID: 12737857

  BACKGROUND: Dietary fibre is thought to protect against colorectal cancer but this view has been challenged by recent prospective and intervention studies that showed no protective effect.
  METHODS: We prospectively examined the association between dietary fibre intake and incidence of colorectal cancer in 519,978 individuals aged 25-70 years taking part in the EPIC study, recruited from ten European countries. Participants completed a dietary questionnaire in 1992-98 and were followed up for cancer incidence. Relative risk estimates were obtained from fibre intake, categorised by sex-specific, cohort-wide quintiles, and from linear models relating the hazard ratio to fibre intake expressed as a continuous variable.
  FINDINGS: Follow-up consisted of 1,939,011 person-years, and data for 1065 reported cases of colorectal cancer were included in the analysis. Dietary fibre in foods was inversely related to incidence of large bowel cancer (adjusted relative risk 0.75 [95% CI 0.59-0.95] for the highest versus lowest quintile of intake), the protective effect being greatest for the left side of the colon, and least for the rectum. After calibration with more detailed dietary data, the adjusted relative risk for the highest versus lowest quintile of fibre from food intake was 0.58 (0.41-0.85). No food source of fibre was significantly more protective than others, and non-food supplement sources of fibre were not investigated.
  INTERPRETATION: In populations with low average intake of dietary fibre, an approximate doubling of total fibre intake from foods could reduce the risk of colorectal cancer by 40%.

PMID: 12737858

PMID: 12699963

  The lower rates of some cancers in Asian countries than in Western countries may be partly because of diet, although the mechanisms are unknown. The aim of this cross-sectional study was to determine whether a plant-based (vegan) diet is associated with a lower circulating level of insulin-like growth factor I (IGF-I) compared with a meat-eating or lacto-ovo-vegetarian diet among 292 British women, ages 20-70 years. The mean serum IGF-I concentration was 13% lower in 92 vegan women compared with 99 meat-eaters and 101 vegetarians (P = 0.0006). The mean concentrations of both serum IGF-binding protein (IGFBP)-1 and IGFBP-2 were 20-40% higher in vegan women compared with meat-eaters and vegetarians (P = 0.005 and P = 0.0008 for IGFBP-1 and IGFBP-2, respectively). There were no significant differences in IGFBP-3, C-peptide, or sex hormone-binding globulin concentrations between the diet groups. Intake of protein rich in essential amino acids was positively associated with serum IGF-I (Pearson partial correlation coefficient; r = 0.27; P < 0.0001) and explained most of the differences in IGF-I concentration between the diet groups. These data suggest that a plant-based diet is associated with lower circulating levels of total IGF-I and higher levels of IGFBP-1 and IGFBP-2.

PMID: 12433724

  Incidence rates for esophageal adenocarcinoma have increased >350% since the mid-1970s. Rates for gastric cardia adenocarcinoma have also increased, although less steeply. This led to the initiation of large population-based case-control studies, particularly in the United States and Sweden, aimed at identifying risk factors for these cancers. Results have been emerging from these studies, with the consistent finding that obesity and gastroesophageal reflux disease are important risk factors for these cancers. Analyses of dietary factors are also available and indicate that diets high in total fat, saturated fat and cholesterol are associated with an increased risk of these cancers, whereas several nutrients, particularly those found in plant foods (fiber, vitamin C, beta-carotene, folate), are associated with a reduced risk. Considering the incidence trends of these cancers and the trends in the prevalence of risk factors, the increasing prevalence of obesity in the United States likely accounts for some of the increased incidence. However, other contributors to the increasing trends have been suggested and will be discussed. Because diet, obesity and gastroesophageal reflux disease may not act independently in contributing to these cancers, current research is attempting to identify associations between the three risk factors and potential mechanisms of action to better understand the etiology of these cancers.

PMID: 12421872

  Cumulative evidence suggests a possible interaction of cooking methods with diet in the pathogenesis of breast cancer. Studies, however, are few and inconsistent. We evaluated the association of animal food intake and degree of browning by deep-frying with breast cancer risk in a population-based case-control study conducted during 1996-1998 among Chinese women in Shanghai, a population with a traditionally low risk of breast cancer. Included in the study were 1459 cases and 1556 age-frequency-matched controls with response rates of 91.1 and 90.3%, respectively. A validated food frequency questionnaire was used to obtain information on usual intake of animal foods and cooking oils and usual cooking methods. Increasing intake of red meat and freshwater fish was related to a moderately elevated risk of breast cancer risk. Stratified analyses showed that the positive association with red meat intake was primarily restricted to those who used deep-frying cooking method, particularly among those who deep-fried foods to well-done (odds ratio, 1.92; 95% confidence interval, 1.30-2.83 for the highest versus the lowest quintile; P for trend, 0.002). On the other hand, high intake of nonhydrogenated soybean cooking oil was related to a reduced risk of breast cancer among women who never deep-fried animal foods (odds ratio, 0.48; 95% confidence interval, 0.28-0.82 for the highest versus the lowest quintile; P for trend, 0.02). The positive association of breast cancer risk with red meat intake, especially well-done red meat, was more pronounced among women with a high body mass index than those without this risk factor, and the test for multiplicative interaction was statistically significant. This study suggests that high intake of deep-fried, well-done red meat may be associated with an increased risk of breast cancer, and the positive association may be modified by body weight. This study also suggests that nonhydrogenated soybean oil, if not used in high-temperature cooking, may be associated with a reduced risk of breast cancer.

PMID: 12223422

  To investigate the role of lifelong vegetarianism on the aetiology of female breast cancer, we conducted a population-based case-control study among South Asian migrant women from the Indian subcontinent resident in England. A total of 240 South Asian breast cancer cases were identified from 2 cancer registries during 1995-1999. For each case, 2 age-matched South Asian controls were randomly selected from the age-sex register of the case practice. Lifelong vegetarians had a slight reduction, although not statistically significant, in the odds of breast cancer relative to lifelong meat-eaters, which persisted after adjustment for socio-demographic and reproductive variables [odds ratio (OR)=0.77; 95% confidence interval (CI)=0.50-1.18]. Analysis by food group revealed no linear trend in the odds of breast cancer with increasing consumption of meat (p=0.10) but the odds were higher for women in the top 75%. In contrast, there were strong inverse trends in the odds of breast cancer with increasing intake of vegetables (p=0.005), pulses (p=0.007) and fibre [non-starch polysaccharides, NSP (p=0.02)], with women in the highest 25% of intake of these foods having about 50% of the odds of those in the lowest ones. Adjustment for intake of vegetables and pulses reverted the odds of breast cancer in lifelong vegetarians relative to lifelong meat-eaters (OR=1.04; 95% CI=0.65-1.68) and attenuated the quartile-specific estimates for meat intake, whereas the inverse trends in the odds of breast cancer with intake of vegetables and pulses remained after adjustment for type of diet or meat intake. These findings suggest that lifelong vegetarianism may be associated with a reduction in the risk of breast cancer through its association with a higher intake of vegetables and pulses. Although it is not possible to exclude the possibility that lifelong meat abstention may also play a role, the findings provide evidence that a diet rich in vegetables and pulses, such as those typically found in South Asian diets, may be protective against this cancer. Copyright 2002 Wiley-Liss, Inc.

PMID: 11979439

  The association between the p53 tumor suppression gene mutation, which is a common event in the development of colon cancer, and dietary and lifestyle factors was evaluated as part of a multicenter case-control study. The p53 mutational status was determined for a total of 1458 cases of colon cancer using single strand conformational polymorphism/sequencing of exons 5-8. The associations between those with mutations and those without were compared with a population-based group of controls (n = 2410). Comparisons were also made between cases with p53 mutations compared with cases without p53 mutations.
  Subjects with a p53 mutation were more likely to consume a Western-style diet compared with controls than were cases who were p53 wild type. Specific components of the diet were also found to be most strongly associated with p53 mutations, including a diet with a high glycemic load as well as foods high in red meat, fast food, and trans-fatty acid (mutation vs control, odds ratio = 1.92 95% CI = 1.47-2.50). Diets with a high glycemic load relative to the lowest intake were found to be significantly associated with missense mutations (OR = 1.69; 95% CI = 1.23-2.33, comparing p53+ to controls, and OR = 1.72; 95% CI = 1.19-2.50, comparing cases p53+ to cases of p53 wild type). Similar findings were seen with diets high in red meat, fast food and trans-fatty acid.
  The authors conclude that components of the Western diet -- namely, red meat and foods that increase glycemic load -- may play an important role in the process of the p53 disease.
  Clinical Commentary
  This important study shows a clear association between specific features of the Western diet and the p53 tumor suppressor gene. Inactivation of the p53 tumor suppressor gene is a common event in the development of colon cancer. The strength of this study lies in the number of subjects studied and the case-control study design, although little information is provided on the dietary methodology used and the quality of the dietary data collected (eg, what was the extent of under-reporting?). It is important to note that the conclusions of the study need to be treated with some caution, i.e. that components of the Western-style diet are associated with the p53 disease pathway. This study provides no indication of the mechanisms involved in this association and the number of confounding factors controlled for were limited. Specific nutrient components, such as total fat intake and levels of particular vitamins and minerals, also were not investigated. This is a useful 'hypothesis-generating' study, and further research is certainly warranted in this area, particularly the role of fruit and vegetables (and other food components) as possible protective factors.

  BACKGROUND The role of diet in the etiology of breast carcinoma has been debated for decades. The ecologic approach generally finds that dietary fat is highly associated with breast carcinoma mortality, with fish intake and solar ultraviolet-B (UV-B) radiation, a source of vitamin D, inversely associated. Case-control and cohort studies generally find a variety of chemical, nonfat dietary, environmental, genetic, lifestyle, and reproductive factors to be important.
  METHODS An ecologic study was conducted using breast carcinoma mortality rates (1989-1996), dietary supply data, and latitude (an index of solar UV-B radiation) from 35 countries.
  RESULTS The fraction of energy derived from animal products (risk) combined with that from vegetable products (risk reduction), followed by solar UV-B radiation and, to a lesser extent, energy derived from alcohol (risk) and fish intake (risk reduction), were found to explain 80% of the variance of breast carcinoma mortality rates. Dietary fat contributed insignificantly in regressions involving the other factors.
  CONCLUSIONS It is hypothesized that animal products are associated with risk for breast carcinoma because they are associated with greater amounts of insulin-like growth factor-1 [IGF-I] and lifetime doses of estrogen. Vegetable products contain several risk reduction components including antioxidants and phytoestrogens. The association with latitude is very likely because of solar UV-B radiation and vitamin D. Alcohol modulates estrogen's effects on breasts. Fish intake is associated with risk reduction through vitamin D and n-3 oils. These results are consistent with those of many case-control and cohort studies but should be assessed in well designed cohort studies.

  New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.

PMID: 11461162

  Statistics compiled by the National Cancer Institute indicate that, between 1935 and 1974, age-adjusted mortality from most 'Western' cancers (those of the breast, colon, prostate, pancreas, ovary, and kidney) rose dramatically in African-Americans. This phenomenon is paralleled by marked increases in the incidence of these cancers in Asia and Southern Europe during the latter 20th century, in conjunction with increased intakes of dietary animal products. A credible case can be made that diets rich in animal products work in various complementary ways to up-regulate serum levels of insulin, free IGF-I, and free sex hormones: hormones that appear to have important promotional activity for Western cancers. It seems likely that dietary animal product intake by black Americans increased substantially during the 20th century, and that this fact is primarily responsible for their concurrent marked increase in mortality from Western cancers. A whole-food vegan diet rich in fruits and vegetables, especially if coupled with regular exercise and smoking avoidance, could be expected to have a remarkably positive impact on African-American cancer risk, reversing the increases in cancer risk incurred during the 20th century. Copyright 2001 Harcourt Publishers Ltd.

PMID: 11461167

  An increased risk of breast cancer has been observed in women who consume "very well-done" meats. Heterocyclic amines are mutagenic and carcinogenic pyrolysis products formed during high temperature cooking of meats. In the present study, human milk samples were analyzed for PhIP, one of the most abundant dietary heterocyclic amine. A protocol was developed with a mixed-mode cation exchange sorbent for the extraction of heterocyclic amines from milk. Milk samples were acquired from healthy Canadian women. With LC/MS analysis and the method of isotope dilution for quantification, levels of PhIP were determined in human milk samples. PhIP was detected in 9 of the 11 milk samples, at levels as high as 59 pg/mL (ppt). No PhIP was detected in the milk of the vegetarian donor. Detection of PhIP in milk indicates that ductal mammary epithelial cells are directly exposed to this carcinogen, suggesting that heterocyclic amines are possible human mammary carcinogens.

PMID: 11712910

  FIBERS: A group of vegetarian subjects have been shown to have a lower risk of cancer of the prostate than a control group. But the exact role of food fiber remains to be determined because plant foods also have an antioxidant effect on their own.
  PLANT PRODUCTS AND EXTRACTS: A compound called PD SPEC has been showed to have antitumor effects both in vitro and in vivo. Evaluated in patients with a cancer escaping hormone control, the clinical response was a lower level of prostate specific antigen (PSA).
  SOYBEANS: Several studies have demonstrated the interesting properties of soybeans. No study has however been able to demonstrate the optimal dose per day. A prospective study is currently under way using a 40 g/day dose.
  OVERALL NUTRITIONAL APPROACH: Several studies are being conducted using a proposed diet where 15% of the total energy intake comes from fat (associated with a low saturated/unsaturated ratio), high fiber content (18 g/100 kcal) and 40 g daily soybean protein. Although large-scale studies with rigorous methodology are lacking, an overall nutritional approach could be an interesting strategy for the management of cancer of the prostate.

PMID: 11317937

  Diets that are low in certain essential amino acids (EAAs), whether owing to low protein content or poor protein quality, tend to down-regulate systemic IGF-I activity, boost thermogenesis, and suppress hepatic capacity for lipogenesis, while promoting hepatic fatty acid oxidation. It is proposed that for each EAA there is a regulatory protein in hepatocytes whose activity is repressed by adequate levels of its EAA; if one (or more) of these regulatory proteins is active, it serves as a signal of EAA deficiency which then mediates the aforementioned effects on IGF-I activity, thermogenesis, and hepatic fatty acid metabolism. Mechanisms which monitor EAA availability likewise play a role in appetite regulation, thus accounting for the fact that spontaneous calorie consumption tends to be lower on high-protein diets. Diets low in protein quantity or quality may decrease insulin secretion, an effect which should contribute to their impact on IGF-I activity and lipid metabolism. The fact that vegans ingest diets that tend to be relatively low in certain EAAs may play a key role in their characteristic leanness and their decreased risk for diabetes, coronary disease, and cancer.

PMID: 11425291

  Agents that inhibit the synthesis of mevalonate or of downstream isoprenoids block the G1-S transition and induce apoptosis in many cell lines; these agents include statins, phenylacetate, and a range of cyclic and acyclic isoprenoids. This cytostatic effect is mediated primarily by decreased availability of dolichol; this deficit impedes the glycosylation of nascent IGF-I receptors, preventing their transfer to the cell surface. In most tissues as well as transformed cell lines, IGF-I activity is crucial for transition to S phase, and also prevents apoptosis. Thus, down-regulation of serum levels of free IGF-I - as may be achieved by caloric restriction, low-fat vegan diets, and various estrogen agonists/antagonists - may represent a useful strategy for preventing and controlling cancer; however, a compensatory up-regulation of tissue expression of IGF-I receptors limits the efficacy of such an approach. Concurrent use of agents that inhibit dolichol synthesis can be expected to prevent an increase in plasma membrane IGF-I receptors, thus potentiating the cancer-retardant efficacy of IGF-I down-regulation. Since dolichol and IGF-I appear to be essential for angiogenesis, these measures may also prove useful for control of pathogenic neovascularization.

PMID: 11133248

  High background levels of phenol and hydroquinone are present in the blood and urine of virtually all individuals, but vary widely. Phenol and hydroquinone have been strongly implicated in producing leukemia associated with benzene exposure, because they reproduce the hematotoxicity of benzene, cause DNA and chromosomal damage found in leukemia, inhibit topoisomerase II, and alter hematopoiesis and clonal selection. The widely varying background levels of phenol and hydroquinone in control individuals stem mainly from direct dietary ingestion, catabolism of tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing foods, cigarette smoking, and the use of some over-the-counter medicines. We hypothesize that these background sources of phenol and hydroquinone and associated adducts play a causal role in producing some forms of de novo leukemia in the general population. This hypothesis is consistent with recent epidemiological findings associating leukemia with diets rich in meat and protein, the use of antibiotics (which change gastrointestinal flora make-up), lack of breastfeeding, and low activity of NAD(P)H quinone oxidoreductase which detoxifies quinones derived from phenol and hydroquinone and protects against benzene hematotoxicity. An attractive feature of our hypothesis is that it may explain why many people who have no known occupational exposures or significant smoking history develop leukemia. The hypothesis predicts that susceptibility to the disease would be related to diet, medicinal intake, genetics and gut-flora composition. The latter two of these are largely beyond our control, and thus dietary modification and reduced use of medicines that elevate phenol levels may be the best intervention strategies for lowering leukemia risk.

PMID: 11243376

  High intake of red meat is associated with increased colon cancer risk. We have shown earlier that this may be due to the high haem content of red meat, because dietary haem increased cytolytic activity of faecal water and colonic epithelial proliferation. Dietary calcium inhibits diet-induced epithelial hyperproliferation. Furthermore, it has been shown that supplemental calcium inhibited the recurrence of colorectal adenomas. Therefore, we studied whether dietary calcium phosphate can exert its protective effects by inhibiting the deleterious effects of haem. In vitro, calcium phosphate precipitated haem and inhibited the haem-induced cytotoxicity. Subsequently, rats were fed diets, differing in haem (0 or 1.3 micromol/g) and calcium phosphate content only (20 or 180 micromol/g). Faeces were collected for biochemical analyses. Cytolytic activity of faecal water was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. In rats fed low calcium diets, dietary haem increased cytolytic activity of faecal water (98 +/- 1 versus 1 +/- 1%, P < 0.001) and the concentration of cations in faeces (964 +/- 31 versus 254 +/- 20 micromol/g), when compared with controls. This indicates that dietary haem increased colonic mucosal exposure to luminal irritants. Colonic epithelial proliferation was increased compared with controls (70 +/- 4 versus 48 +/- 8 d.p.m./microg DNA, P < 0.001). This was accompanied by metabolism of the ingested haem and solubilization of haem compounds in the faecal water. A high calcium diet largely prevented this metabolism and solubilization. It also inhibited the haem-induced cytolytic activity of faecal water and increase in faecal cation concentration. In accordance, the haem-induced colonic epithelial hyperproliferation was prevented. We therefore suggest that dietary calcium phosphate acts as a chemopreventive agent in colon carcinogenesis by inhibiting the cytolytic and hyperproliferative effects of dietary haem.

PMID: 11577005

  Incidence rates for adenocarcinoma of the esophagus and gastric cardia have been rising rapidly. We examined nutrient intake as a risk factor for esophageal and gastric cancers in a population-based case-control study in Connecticut, New Jersey, and western Washington state. Interviews were completed for cases with histologically confirmed esophageal adenocarcinoma (n = 282), adenocarcinoma of the gastric cardia (n = 255), esophageal squamous cell carcinoma (n = 206), and noncardia gastric adenocarcinoma (n = 352), along with population controls (n = 687). Associations between nutrient intake and risk of cancer were estimated by adjusted odds ratios (ORs), comparing the 75th versus the 25th percentile of intake. The following nutrients were significantly inversely associated with risk of all four tumor types: fiber, beta-carotene, folate, and vitamins C and B6. In contrast, dietary cholesterol, animal protein, and vitamin B12 were significantly positively associated with risk of all four tumor types. Dietary fat [OR, 2.18; 95% confidence interval (CI), 1.27-3.76] was significantly associated with risk of esophageal adenocarcinoma only. Dietary nitrite (OR, 1.65; 95% CI, 1.26-2.16) was associated with noncardia gastric cancer only. Vitamin C supplement use was associated with a significantly lower risk for noncardia gastric cancer (OR, 0.60; 95% CI, 0.41-0.88). Higher intake of nutrients found primarily in plant-based foods was associated with a reduced risk of adenocarcinomas of the esophagus and gastric cardia, whereas higher intake of nutrients found primarily in foods of animal origin was associated with an increased risk.

PMID: 1158813

  FIBERS: A group of vegetarian subjects have been shown to have a lower risk of cancer of the prostate than a control group. But the exact role of food fiber remains to be determined because plant foods also have an antioxidant effect on their own.
  PLANT PRODUCTS AND EXTRACTS: A compound called PD SPEC has been showed to have antitumor effects both in vitro and in vivo. Evaluated in patients with a cancer escaping hormone control, the clinical response was a lower level of prostate specific antigen (PSA).
  SOYBEANS: Several studies have demonstrated the interesting properties of soybeans. No study has however been able to demonstrate the optimal dose per day. A prospective study is currently under way using a 40 g/day dose.
  OVERALL NUTRITIONAL APPROACH: Several studies are being conducted using a proposed diet where 15% of the total energy intake comes from fat (associated with a low saturated/unsaturated ratio), high fiber content (18 g/100 kcal) and 40 g daily soybean protein. Although large-scale studies with rigorous methodology are lacking, an overall nutritional approach could be an interesting strategy for the management of cancer of the prostate.

PMID: 11317937

  New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.

PMID: 1146116

  We tested the effects of feeding a diet very high in fiber from fruit and vegetables. The levels fed were those, which had originally inspired the dietary fiber hypothesis related to colon cancer and heart disease prevention and also may have been eaten early in human evolution. Ten healthy volunteers each took 3 metabolic diets of 2 weeks duration. The diets were: high-vegetable, fruit, and nut (very-high-fiber, 55 g/1,000 kcal); starch-based containing cereals and legumes (early agricultural diet); or low-fat (contemporary therapeutic diet). All diets were intended to be weight-maintaining (mean intake, 2,577 kcal/d). Compared with the starch-based and low-fat diets, the high-fiber vegetable diet resulted in the largest reduction in low-density lipoprotein (LDL) cholesterol (33% +/- 4%, P <.001) and the greatest fecal bile acid output (1.13 +/- 0.30 g/d, P =.002), fecal bulk (906 +/- 130 g/d, P <.001), and fecal short-chain fatty acid outputs (78 +/- 13 mmol/d, P <.001). Nevertheless, due to the increase in fecal bulk, the actual concentrations of fecal bile acids were lowest on the vegetable diet (1.2 mg/g wet weight, P =.002). Maximum lipid reductions occurred within 1 week. Urinary mevalonic acid excretion increased (P =.036) on the high-vegetable diet reflecting large fecal steroid losses. We conclude that very high-vegetable fiber intakes reduce risk factors for cardiovascular disease and possibly colon cancer. Vegetable and fruit fibers therefore warrant further detailed investigation. Copyright 2001 by W.B. Saunders Company

PMID: 11288049

   It has been postulated that high intakes of animal fat and protein and low intakes of fiber, calcium, and antioxidants increase the risk of colorectal cancer. Whether specific types of protein such as that from red meat are important, and whether vegetables might be key protective factors will also be considered in this study. Dietary intake over the past year was studied according to the diet history method by means of a case-control study in 184 cases and matched controls. After adjustment for energy, relative weight, and social class, no associations were found for fat or protein in comparison with either control group. Unexpectedly, carbohydrate intake was inversely related with adenoma risk, the RR being 0.29 (0.10-0.81) for quintile 5 versus 1 in comparison with hospital controls. None of the antioxidants showed a significant protective effect except beta-carotene intake in comparison with hospital controls, the RR being 0.24 (0.11-0.50) for the highest versus the lowest quintile. There was, however, a statistically significant positive association between adenomas and meat consumption with the RR for the highest versus the lowest quintile of intake being 3.6 (1.7-7.5) in comparison with hospital controls and 4.4 (1.6-12.1) in comparison with population controls. Our data support the protective role for carbohydrate intake and of beta-carotene intake in the etiology of colorectal adenomas and show a strong increased risk for developing adenomas in those with high meat intake.

PMID: 11270799

  BACKGROUND: Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer.
  METHODS: We conducted a nested case-control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided.
  RESULTS: Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218-240 ng/mL] versus 214 ng/mL [95% CI = 208-221 ng/mL]; P =.02) and IGFBP-3 (2611 ng/mL [95% CI = 2518-2704 ng/mL] versus 2498 ng/mL [95% CI = 2437-2560 ng/mL]; P =.04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (P:(for trend) =.02) and IGFBP-3 (P(for trend) =.03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (P:(for trend) =.01), whereas the risk associated with increased IGFBP-3 was lower (P(for trend) =.44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin.
  CONCLUSIONS: Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer. [Note: IGF-I is present in cow milk; see the NotMilk site for more info.]

PMID: 11106682

  Typically, cancer is caused by the interaction of genetic and environmental factors. In colorectal carcinogenesis, diet and nutritional habits are the most important external risk determinants. Allelic polymorphisms of certain metabolizing enzymes may have an influence on cancer risk by modifying the concentration of active carcinogenic compounds in the body. In the present study we investigated the interaction between nutritional and genetic susceptibility factors in human colon carcinogenesis. Healthy volunteers were divided into four groups, based on allelic polymorphisms of N-acetyltransferase 2 and glutathione-S-transferase M1 enzymes. Comet assay was used to determine the level of DNA strand breaks in exfoliated colorectal mucosal cells, following a 2-day vegetarian diet, and after switching to a 2-day 'high-meat' diet. The 'high-meat' diet statistically significantly increased the amount of single-strand breaks in rapid acetylators and among individuals with a GSMT1 + genotype, while it caused only a slight and not significant increase in the other groups. Our study emphasizes the importance of using susceptibility markers in cancer epidemiology, since environmental effects are strongly modified by these genetic factors.  [Note: the gene-damaging effects were immediate - ljf]

PMID: 11201682

 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine formed in meat and fish during cooking and can be used as a model compound for this class of chemicals possibly involved in human carcinogenesis. Knowing the exposure to heterocyclic amines is important for establishing their role in human diseases. Serum albumin (SA) and globin (Gb) adducts were first tested as biomarkers of exposure to PhIP in male Fischer 344 rats given oral doses of 0.1, 0.5, 1 and 10 mg/kg. Blood samples were collected 24 hr after treatment and PhIP released from SA and Gb after acidic hydrolysis was analyzed by gas chromatography-mass spectrometry or liquid chromatography-tandem mass spectrometry. PhIP-SA and Gb adducts increased linearly with the dose. Studies on 35 volunteers with different dietary habits exhibited that diet was a major determinant in the formation of both adducts. PhIP-SA adducts were significantly higher in meat consumers than in vegetarians (6.7 +/- 1.6 and 0.7 +/- 0.3 fmol/mg SA; respectively, mean +/- SE; p = 0.04, Mann-Whitney U test). The Gb adduct pattern was quantitatively lower but paralleled SA (3 +/- 0.8 in meat consumers and 0.3 +/- 0.1 in vegetarians). PhIP-SA adducts were no different in smokers and in non-smokers. The results show for the first time that PhIP-blood protein adducts are present in humans not given the synthetic compound. Both biomarkers appear to be suitable for assessing dietary exposure and internal PhIP dose and may be promising tools for studying the role of heterocyclic amines in the etiology of colon cancer and other diseases. Copyright 2000 Wiley-Liss, Inc.

PMID: 10962432

  High intake of red meat is associated with an increased risk of colon cancer. It has been suggested that fat from red meat is responsible, because high fat intake increases the concentration of cytotoxic lipids in the colon. Experimental studies have not unequivocally supported such a role for fat, however. Recently, we showed that dietary haem, which is abundant in red meat, increased colonic cytotoxicity and epithelial proliferation. In this study, we wanted to clarify whether dietary fat affects colon cancer risk by itself or by modulating the detrimental effects of haem on the colonic epithelium. Rats were fed control or haem-supplemented diets with 10%, 25% or 40% of the energy derived from fat for 14 days. Faeces were collected for biochemical analyses. Colonic cytotoxicity was determined from the degree of lysis of erythrocytes by faecal water. Colonic epithelial proliferation was measured in vivo using [(3)H]thymidine incorporation. Increasing the fat content of the control diets stimulated faecal disposal of both fatty acids and bile acids. It also increased the concentration of fatty acids, but not that of bile acids, in faecal water in control rats. The cytolytic activity of faecal water and colonic epithelial proliferation were unaffected. Dietary haem increased faecal cation content and cytolytic activity of faecal water at all fat levels, suggesting that the colonic mucosa was exposed to high amounts of luminal irritants. This effect was smaller in rats on the low-fat diet. Dietary haem also increased colonic epithelial proliferation at all fat levels. The haem-induced effects were independent of fatty acids or bile acids in the faecal water. In western societies, 30-40% of ingested energy is supplied by dietary fat, so our results suggest that the association between consumption of red meat and risk of colon cancer is mainly due to its haem content, and is largely independent of dietary fat content.

PMID: 11023550

  Mean serum insulin-like growth factor-I [IGF-I] was 9% lower in 233 vegan men than in 226 meat-eaters and 237 vegetarians (P = 0.002). Vegans had higher testosterone levels than vegetarians and meat-eaters, but this was offset by higher sex hormone binding globulin, and there were no differences between diet groups in free testosterone, androstanediol glucuronide or luteinizing hormone.

PMID: 10883675

  BACKGROUND: Hydrogen sulfide is a luminally acting, bacterially derived cell poison that has been implicated in ulcerative colitis. Sulfide generation in the colon is probably driven by dietary components such as sulfur-containing amino acids (SAAs) and inorganic sulfur (eg, sulfite).
  OBJECTIVE: We assessed the contribution of SAAs from meat to sulfide production by intestinal bacteria with use of both a model culture system in vitro and an in vivo human feeding study.
  DESIGN: Five healthy men were housed in a metabolic suite and fed a sequence of 5 diets for 10 d each. Meat intake ranged from 0 g/d with a vegetarian diet to 600 g/d with a high-meat diet. Fecal sulfide and urinary sulfate were measured in samples collected on days 9 and 10 of each diet period. Additionally, 5 or 10 g bovine serum albumin or casein/L was added to batch cultures inoculated with feces from 4 healthy volunteers. Concentrations of sulfide, ammonia, and Lowry-reactive substances were measured over 48 h.
  RESULTS: Mean (+/-SEM) fecal sulfide concentrations ranged from 0.22 +/- 0.02 mmol/kg with the 0-g/d diet to 3.38 +/- 0.31 mmol/kg with the 600-g/d diet and were significantly related to meat intake (P: < 0.001). Sulfide formation in fecal batch cultures supplemented with both bovine serum albumin and casein correlated with protein digestion, as measured by the disappearance of Lowry-reactive substances and the appearance of ammonia.
  CONCLUSION: Dietary protein from meat is an important substrate for sulfide generation by bacteria in the human large intestine.

PMID: 11101476

  Ursolic acid (UA) is a pentacyclic triterpenoid compound which occurs naturally in a large variety of vegetarian foods, medicinal herbs and plants. In the present study, ursolic acid was found to decrease cell viability in human lymphoma Daudi cells in a dose-dependent manner. UA also induced morphological changes in cells as well as loss of membrane asymmetry, DNA fragmentation and nuclei condensation, indicating that the mechanism by which UA induced cell death was through apoptosis. Treatment with UA increased intracellular Ca2+ levels. Use of Ca2+ channel inhibitors like verapamil blocked this Ca2+ influx and also the triggering of apoptosis. We hypothesized that the binding of UA to glucocorticoid receptors and the Ca2+ currents induced constituted the first steps of apoptosis.

PMID: 11129737

  Meat intake has been positively associated with risk of digestive tract cancers in several epidemiological studies, while data on the relation of meat intake with cancer risk at most other sites are inconsistent. The overall data set, derived from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996, included the following incident, histologically confirmed neoplasms: oral cavity, pharynx and esophagus (n = 497), stomach (n = 745), colon (n = 828), rectum (n = 498), liver (n = 428), gallbladder (n = 60), pancreas (n = 362), larynx (n = 242), breast (n = 3,412), endometrium (n = 750), ovary (n = 971), prostate (n = 127), bladder (n = 431), kidney (n = 190), thyroid (n = 208), Hodgkin's disease (n = 80), non-Hodgkin's lymphomas (n = 200) and multiple myelomas (n = 120). Controls were 7,990 patients admitted to hospital for acute, non-neoplastic conditions unrelated to long-term modifications in diet. The multivariate odds ratios (ORs) for the highest tertile of red meat intake (>/=7 times/week) compared with the lowest (Thus, reducing red meat intake might lower the risk for several common neoplasms. Copyright 2000 Wiley-Liss, Inc.

PMID: 10760833

  There is consistent and strong evidence that a high risk of colorectal cancer is associated with obesity and with a low intake of vegetables, of whole grain cereals and of fish. Many other food groups or nutrients have been associated with this cancer, but the evidence for them is inconsistent and therefore untenable. Vegetables contain a wide range of protective agents that protect against cancer at many other sites as well as the large bowel. The same is true of whole grain cereals; these can also protect against colorectal cancer by mechanisms specific to the large bowel. Fish are rich in n-3 polyunsaturated fatty acids that are thought to protect the colon against malignancy via the prostaglandin pathway. Overweight is the result of an excess of energy intake over energy output, and there is good evidence to suggest that overweight might be a surrogate measure of lack of exercise.

PMID: 10772423

  In order to examine the risks of cancer of the upper aerodigestive tract associated with food groups, a case-control study was conducted in Uruguay in the period January 1996-December 1997. All patients afflicted with cancer of the oral cavity, pharynx larynx, and esophagus, were included in the study. Cases were frequency matched with hospitalized patients on age, sex, residence, and urban/rural status. A strong association with red meat intake was observed (OR 2.4, 95% CI 1.2-4.8), whereas vegetables fruits and legumes were associated with an inverse association (OR for fruits 0.3, 95% CI 0.2-0.6). Salted meat, a possible source of nitrosamines, was associated with an increased risk of 60% for esophageal cancer. Possible mechanisms for these findings are discussed.

PMID: 10211305

  OBJECTIVE: To investigate whether the rarity of colon cancer in black Africans (prevalence, < 1:100,000) can be accounted for by dietary factors considered to reduce risk, and by differences in colonic bacterial fermentation.
  METHODS: Samples of the adult black South African population were drawn from several rural and urban regions. Food consumption was assessed by home visits, food frequency questionnaires, computerized analysis of 72-h dietary recall, and blood sampling. Colonic fermentation was measured by breath H2 and CH4 response to a traditional meal, and to 10-g of lactulose. Cancer risk was estimated by measurement of epithelial proliferation indices (Ki-67 and BrdU) in rectal mucosal biopsies. Results were evaluated by comparison to measurements in high-risk white South Africans (prevalence, 17:100,000).
  RESULTS: Epithelial proliferation was significantly lower in rural and urban blacks than whites. The diets of all the black subgroups were characterized by a low animal product and high boiled maize-meal content, whereas whites consumed more fresh animal products, cheese, and wheat products. Blacks consumed below RDA quantities of fiber (43% of RDA), vitamin A (78%), C (62%), folic acid (80%) and calcium (67%), whereas whites consumed more animal protein (177% of RDA) and fat (153%). Fasting and food-induced breath methane production was two to three times higher in blacks.
  CONCLUSIONS: The low prevalence of colon cancer in black Africans cannot be explained by dietary "protective" factors, such as, fiber, calcium, vitamins A, C and folic acid, but may be influenced by the absence of "aggressive" factors, such as excess animal protein and fat, and by differences in colonic bacterial fermentation.

  BACKGROUND: Several uncertainties remain with respect to the role of intake of fat and/or total energy in the etiology of cancer of the breast and colon-rectum.
  PATIENTS AND METHODS: Between 1991 and 1996, 2569 women with incident breast cancer (median age: 55 years), 1953 subjects with cancer of the colon-rectum (median age = 62), and 5155 hospital controls were interviewed in six Italian areas. The validated food frequency questionnaire included questions on 78 foods and recipes and specific questions on individual fat intake pattern.
  RESULTS: Significant trends of increasing breast and colorectal cancer risk with increasing intake emerged for bread and pasta, pork and processed meats and potatoes (breast cancer only), cakes and desserts (colon-rectum cancers only), and refined sugar. Most vegetables were inversely associated with cancer of the colon and rectum, whereas only carrots and raw vegetables seemed to lower breast cancer risk. High fruit intake was associated only with a reduction of rectal cancer. Total energy intake was directly associated with all cancer sites. Among macronutrients, high intake of starch and saturated fat seemed to lead to an increase of cancer risk. High intakes of polyunsaturated fatty acids (chiefly derived from olive oil and seed oils) were protective. Among micronutrients, beta-carotene, vitamin E, and calcium showed inverse associations with breast and colorectal cancer risk.
  CONCLUSIONS: An excess of energy intake, particularly from refined bread and pasta, can be an unfavourable feature of the Mediterranean diet, in the presence of a sedentary lifestyle.

PMID: 10676554

  Results associating diet with chronic disease in a cohort of 34192 California Seventh-day Adventists are summarized. Most Seventh-day Adventists do not smoke cigarettes or drink alcohol, and there is a wide range of dietary exposures within the population. About 50% of those studied ate meat products <1 time/wk or not at all, and vegetarians consumed more tomatoes, legumes, nuts, and fruit, but less coffee, doughnuts, and eggs than did nonvegetarians. Multivariate analyses showed significant associations between beef consumption and fatal ischemic heart disease (IHD) in men [relative risk (RR) = 2.31 for subjects who ate beef > or =3 times/wk compared with vegetarians], significant protective associations between nut consumption and fatal and nonfatal IHD in both sexes (RR approximately 0.5 for subjects who ate nuts > or =5 times/wk compared with those who ate nuts <1 time/wk), and reduced risk of IHD in subjects preferring whole-grain to white bread. The lifetime risk of IHD was reduced by approximately 31% in those who consumed nuts frequently and by 37% in male vegetarians compared with nonvegetarians. Cancers of the colon and prostate were significantly more likely in nonvegetarians (RR of 1.88 and 1.54, respectively), and frequent beef consumers also had higher risk of bladder cancer. Intake of legumes was negatively associated with risk of colon cancer in nonvegetarians and risk of pancreatic cancer. Higher consumption of all fruit or dried fruit was associated with lower risks of lung, prostate, and pancreatic cancers. Cross-sectional data suggest vegetarian Seventh-day Adventists have lower risks of diabetes mellitus, hypertension, and arthritis than nonvegetarians. Thus, among Seventh-day Adventists, vegetarians are healthier than nonvegetarians but this cannot be ascribed only to the absence of meat.

PMID: 10479227

  Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets coupled with exercise training; such regimens also tend to markedly improve diabetic control and lower elevated blood pressure. Risk of many other degenerative disorders may be decreased in vegans, although reduced growth factor activity may be responsible for an increased risk of hemorrhagic stroke. By altering the glucagon/insulin balance, it is conceivable that supplemental intakes of key non-essential amino acids could enable omnivores to enjoy some of the health advantages of a vegan diet. An unnecessarily high intake of essential amino acids--either in the absolute sense or relative to total dietary protein--may prove to be as grave a risk factor for 'Western' degenerative diseases as is excessive fat intake.

PMID: 10687887

  We review the beneficial and adverse effects of vegetarian diets in various medical conditions. Soybean-protein diet, legumes, nuts and soluble fibre significantly decrease total cholesterol, low-density lipoprotein cholesterol and triglycerides. Diets rich in fibre and complex carbohydrate, and restricted in fat, improve control of blood glucose concentration, lower insulin requirement and aid in weight control in diabetic patients. An inverse association has been reported between nut, fruit, vegetable and fibre consumption, and the risk of coronary heart disease. Patients eating a vegetarian diet, with comprehensive lifestyle changes, have had reduced frequency, duration and severity of angina as well as regression of coronary atherosclerosis and improved coronary perfusion. An inverse association between fruit and vegetable consumption and stroke has been suggested. Consumption of fruits and vegetables, especially spinach and collard green, was associated with a lower risk of age-related ocular macular degeneration. There is an inverse association between dietary fibre intake and incidence of colon and breast cancer as well as prevalence of colonic diverticula and gallstones. A decreased breast cancer risk has been associated with high intake of soy bean products. The beneficial effects could be due to the diet (monounsaturated and polyunsaturated fatty acids, minerals, fibre, complex carbohydrate, antioxidant vitamins, flavanoids, folic acid and phytoestrogens) as well as the associated healthy lifestyle in vegetarians. There are few adverse effects, mainly increased intestinal gas production and a small risk of vitamin B12 deficiency.

PMID: 10627874

  The intake of a Western diet with a high amount of red meat is associated with a high risk for colon cancer. We hypothesize that heme, the iron carrier of red meat, is involved in diet-induced colonic epithelial damage, resulting in increased epithelial proliferation. Rats were fed purified control diets, or purified diets supplemented with 1.3 micromol/g of hemin (ferriheme), protoporphyrin IX, ferric citrate, or bilirubin (n = 8/group) for 14 days. Feces were collected for biochemical analyses. Fecal cytotoxicity was determined from the degree of lysis of erythrocytes by fecal water. Colonic epithelial proliferation was measured in vivo using [3H]thymidine incorporation into colonic mucosa. The colonic epithelial proliferation in heme-fed rats was significantly increased compared to control rats [55.2 +/- 5.8 versus 32.6 +/- 6.3 dpm/microg DNA (mean +/- SE); P < 0.05]. The fecal water of the heme group was highly cytotoxic compared to the controls (90 +/- 2% versus 2 +/- 1%; P < 0.001), although the concentrations of cytotoxic bile acids and fatty acids were significantly lower. Organic iron was significantly increased compared to the controls (257 +/- 26 versus 80 +/- 21, microM; P < 0.001). Spectrophotometric analyses suggest that this organic iron is heme-associated. Thiobarbituric acid-reactive substances were greatly increased in the fecal water of heme-fed rats compared to the controls (177 +/- 12 versus 59 +/- 7 microM; P < 0.05). Heme itself could not account for the increased cytotoxicity because the addition of heme to the fecal water of the control group, which was equimolar to the organic iron content of the fecal water of the heme group, did not influence the cytotoxicity. Hence, an additional heme-induced cytotoxic factor is involved, which may be modulated by the generation of luminal-reactive oxygen species. Protoporphyrin IX, ferric citrate, and bilirubin did not increase proliferation and cytotoxicity. In conclusion, dietary heme leads to the formation of an unknown, highly cytotoxic factor in the colonic lumen. This suggests that, in heme-fed rats, colonic mucosa is damaged by the intestinal contents. This results in a compensatory hyperproliferation of the epithelium, which supposedly increases the risk for colon cancer.

PMID: 10582688

  The age adjusted incidence of cancer has increased on average 1% annually since the beginning of this century, and cancer is now one of the most prevalent causes of death. Diet is suggested to be responsible for about 30-70% of all cancer cases. The heterocyclic amines (HCA) produced during processing of meats and fish at temperatures above 150 degrees C are candidate dietary causes. Amounts in food range from less than 1 ng/g in cooked meat or fish up to over 300 ng/g in well done flame grilled chicken breast meat. The most important parameters determining HCA amounts are cooking temperature and cooking time. 20 different HCAs are identified from cooked or grilled meats and fish. HCAs are causing cancer in various organs in mice, rats and cynomolgus monkeys. It is of interest to note that in rats, PhIP, the most abundant heterocyclic amine in cooked food, causes colon, prostate and mammary cancer, which are the most prevalent cancers in humans. Epidemiological studies show a correlation between intake of red meat and colon, mammary and prostate cancer. Based on the adverse effects of HCA, a reduced intake is recommended and practical advice on how this can be done is given.

PMID: 10025205

  OBJECTIVES: To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States.
  METHODS: Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer.
  RESULTS: Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers = 0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers = 0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR = 2.7 for blacks and 1.5 for whites) and processed meat (OR = 1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls.
  CONCLUSIONS: In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men.

PMID: 9934713

  Workers in the meat industry are exposed to viruses that cause leukemia and lymphoma in cattle and chickens, and also to carcinogenic chemical agents. This case-control study, nested in a cohort of members of a meatcutters' union in Baltimore, Maryland, investigated whether occupational exposures are associated with death from tumors of the hemopoietic and lymphatic systems. Cases of these tumors represent all deaths which occurred in the cohort between 1949 and 1980. Excess risks of tumors of the hemopoietic and lymphatic systems were observed throughout the meat industry, except in meatpacking plants. Slaughtering activities involving heavy exposure to oncogenic viruses were strongly associated with these tumors, especially with lymphomas. Thus, elevated risks were observed for butchers who killed animals (odds ratio (OR) = 5.3, 95% confidence interval (CI) 1.0-27.0); workers in chicken-slaughtering plants (OR = 3.3, 95% CI 0.8-13.1); and workers in cattle/sheep/pig abattoirs (OR = 2.8, 95% CI 0.8-9.5). Among supermarket workers, wrapping meat (mainly a female activity) was associated with increased risk of tumors of the hemopoietic and lymphatic systems (OR = 3.8, 95% CI 1.0-14.3), with the odds of both lymphomas and tumors of the myeloid stem cell being elevated. On the other hand, meatcutting in supermarkets (almost exclusively a male activity) was associated with multiple myeloma; the odds ratio for men was 18.0 (95% CI 1.6-207.5), with no myeloma cases being recorded in women. These associations persisted after limited control for exposures outside the industry that have also been observed to be associated with excess risk, such as exposure to pesticides, working/living on pig farms, and exposure to X-rays. The findings provide evidence that workers in the meat industry may be at elevated risk of tumors of the hemopoietic and lymphatic systems. Further studies with larger sample sizes are needed to identify more conclusively which exposures play an etiologic role in the occurrence of the different histologic types of these tumors.

PMID: 9554414

  OBJECTIVES: To update the cancer mortality patterns among Iowa (United States) farmers for the years 1987-93 and compare these results with those previously reported for 1971-86 as well as relate the PMR patterns to risk-factor survey data.
  METHODS: We extracted usual occupation and cause of death from 88,090 Iowa death certificates for White males aged 20 and older for the years 1987-93. Proportional mortality ratios (PMR), adjusted for age, and 95 percent confidence intervals (CI) were calculated using deaths among nonfarmers to generate expected numbers. We compared lifestyle profiles for farmers and nonfarmers using male controls (n = 1,596) from a population-based case-control study conducted in Iowa from 1986-89.
  RESULTS: Iowa farmers had deficit PMRs for all-cause cancer mortality (PMR = 0.92, CI = 0.90-0.94) and for lung (PMR = 0.70, CI = 0.66-0.73), liver (PMR = 0.65, CI = 0.50-0.86), and other cancer sites strongly related to smoking and alcohol use. Farmers at all ages had excess deaths for cancers of the prostate (PMR = 1.26, CI = 1.19-1.33), rectum (PMR = 1.29, CI = 1.07-1.56), brain (PMR = 1.10, CI = 0.92-1.32), multiple myeloma (PMR = 1.17, CI = 0.98-1.40), non-Hodgkin's lymphoma (PMR = 1.09, CI = 0.96-1.23), and Hodgkin's disease (PMR = 1.62, CI = 1.04-2.54). Younger farmers (aged 20 to 64 years) had excess deaths for colon cancer (PMR = 1.52, CI =1.26-1.85) and skin melanoma (PMR = 1.60, CI = 1.07-2.38), while older farmers (aged 65+ years) had excess deaths for cancers of the pancreas (PMR = 1.18, CI = 1.04-1.34), lip (PMR = 1.58, CI = 0.59-4.21), and leukemia (PMR = 1.26, CI = 1.09-1.46). Since the 1970s, the PMR for stomach cancer has declined to expected values, while the PMRs for prostate, large intestine, pancreas, and Hodgkin's disease have increased; PMRs for other sites are consistent with earlier data. A survey from 1986-89 showed that farmers, compared with nonfarmers, smoked less, used less alcohol, had less formal education, and consumed more total calories, and calories from protein, fat, and meat while consuming fewer calories from fruits and vegetables.
  CONCLUSIONS: Iowa farmers continue to be at elevated risk of mortality due to certain cancers, and, of particular interest, the risk for prostate and colon cancer appears to be increasing since 1970.

PMID: 9684711

  OBJECTIVE: Some epidemiological studies suggest that diets high in fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Since meat consumption is correlated with the intake of saturated fat and cholesterol, we investigated the role of meat intake and cooking practices in relation to lung cancer risk.
  METHODS: A population-based case-control study of both non-smoking and smoking women was conducted in Missouri. A 100-item food frequency questionnaire (FFQ) with detailed questions on meat consumption was completed by 593 cases and 623 frequency matched controls. We estimated quantity of meat eaten (grams/day) according to cooking method, and doneness level. Odds ratios (ORs) and 95% confidence intervals (C.I.s) were calculated using logistic regression. Multivariate models included age, packyears of smoking, body mass index (BMI, kg/m2), education, and intake of calories, fat, fruit/fruit juices, and vegetables.
  RESULTS: When comparing 90th and 10th percentiles, lung cancer risk increased for total meat consumption (OR = 1.6, C.I. 1.1-2.4), red meat (OR = 1.8, C.I., 1.2-2.7), well-done red meat (OR = 1.5, C.I.s, 1.1-2.1) and fried red meat (OR = 1.5, C.I., 1.1-2.0). The odds ratios for 5th vs. 1st quintiles using the categorical variable for well-done red meat and fried red meat were essentially the same as reported above; however, the increase in risk was associated mainly with the 5th quintile. The ORs for a 10-gram increase in consumption were, 1.04 for total meat, 1.06 for red meat, 1.08 for well done red meat, and 1.09 for fried red meat.
  CONCLUSIONS: Consumption of red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer.

PMID: 10189048

  OBJECTIVE. To estimate the medical costs that are attributable to the health effects of meat consumption.
  METHODS. The prevalence of hypertension, heart disease, cancer, diabetes, gallstones, obesity, and foodborne illness among omnivores and vegetarians are compared in studies that have controlled for other lifestyle factors, and the corresponding attributable medical costs are calculated in 1992 dollars.
  RESULTS. Direct health care costs attributable to meat consumption are estimated to be +2.8-8.5 billion for hypertension, +9.5 billion for heart disease, +0-16.5 billion for cancer, +14.0-17.1 billion for diabetes, +0.2-2.4 billion for gallbladder disease, +1.9 billion for obesity-related musculoskeletal disorders, and +0.2-5.5 billion for foodborne illness. The total direct medical costs attributable to meat consumption for 1992 are estimated at +28.6-61.4 billion.
  CONCLUSION. Health care costs attributable to meat consumption are quantifiable and substantial.

PMID: 8610089

  The questions of whether and how N-nitroso compounds (NOC) may be inducing cancer in humans are discussed. The principal subjects covered include nitrite-derived alkylating agents that are not NOC, reasons for the wide tissue specificity of carcinogenesis by NOC, the acute toxicity of nitrosamines in humans, mechanisms of in vivo formation of NOC by chemical and bacterial nitrosation in the stomach and via nitric oxide (NO) formation during inflammation, studies on nitrite esters, use of the nitrosoproline test to follow human gastric nitrosation, correlations of nitrate in food and water with in vivo nitrosation and the inhibition of gastric nitrosation by vitamin C and polyphenols. Evidence that specific cancers are caused by NOC is reviewed for cancer of the stomach, esophagus, nasopharynx, urinary bladder in bilharzia and colon. I review the occurrence of nitrosamines in tobacco products, nitrite-cured meat (which might be linked with childhood leukemia and brain cancer) and other foods, and in drugs and industrial situations. Finally, I discuss clues from mutations in ras and p53 genes in human tumors about whether NOC are etiologic agents and draw some general conclusions.

PMID: 7600541

  The association between cured and broiled meat consumption by the mother during pregnancy and by the child was examined in relation to childhood cancer. Five meat groups (ham, bacon, or sausage; hot dogs; hamburgers; bologna, pastrami, corned beef, salami, or lunch meat; charcoal broiled foods) were assessed. Exposures among 234 cancer cases (including 56 acute lymphocytic leukemia [ALL], 45 brain tumor) and 206 controls selected by random-digit dialing in the Denver, Colorado (United States) standard metropolitan statistical area were compared, with adjustment for confounders. Maternal hot-dog consumption of one or more times per week was associated with childhood brain tumors (odds ratio [OR] = 2.3, 95 percent confidence interval [CI] = 1.0-5.4). Among children, eating hamburgers one or more times per week was associated with risk of ALL (OR = 2.0, CI = 0.9-4.6) and eating hot dogs one or more times per week was associated with brain tumors (OR = 2.1, CI = 0.7-6.1). Among children, the combination of no vitamins and eating meats was associated more strongly with both ALL and brain cancer than either no vitamins or meat consumption alone, producing ORs of two to seven. The results linking hot dogs and brain tumors (replicating an earlier study) and the apparent synergism between no vitamins and meat consumption suggest a possible adverse effect of dietary nitrites and nitrosamines.

PMID: 8167261

  The relation between the intake of certain food items thought to be precursors or inhibitors of N-nitroso compounds (NOC) and risk of leukemia was investigated in a case-control study among children from birth to age 10 years in Los Angeles County, California (United States). Cases were ascertained through a population-based tumor registry from 1980 to 1987. Controls were drawn from friends and by random-digit dialing. Interviews were obtained from 232 cases and 232 controls. Food items of principal interest were: breakfast meats (bacon, sausage, ham); luncheon meats (salami, pastrami, lunch meat, corned beef, bologna); hot dogs; oranges and orange juice; and grapefruit and grapefruit juice. We also asked about intake of apples and apple juice, regular and charcoal broiled meats, milk, coffee, and coke or cola drinks. Usual consumption frequencies were determined for both parents and the child. When the risks were adjusted for each other and other risk factors, the only persistent significant associations were for children's intake of hot dogs (odds ratio [OR] = 9.5, 95 percent confidence interval [CI] = 1.6-57.6 for 12 or more hot dogs per month, trend P = 0.01), and fathers' intake of hot dogs (OR = 11.0, CI = 1.2-98.7 for highest intake category, trend P = 0.01). There was no evidence that fruit intake provided protection. While these results are compatible with the experimental animal literature and the hypothesis that human NOC intake is associated with leukemia risk, given potential biases in the data, further study of this hypothesis with more focused and comprehensive epidemiologic studies is warranted.

PMID: 8167267

  The study assessed mortality and morbidity risks as related to nutritional status of moderate and strict vegetarians in Germany. The total cohort of 1904 self-identified persons was followed up for 11 y. Compared with national mortality rates for Federal Republic of Germany, the observed deaths for all causes were below expectation by a factor of 0.44 for men and 0.53 for women. The mortality for colon cancer was reduced [standardized mortality ration (SMR 44.1 for men and 77.9 for women]. No deaths were observed from rectal cancer. A vegetarian lifestyle of long duration (> or = 20 y) was associated with decreased overall and cancer mortality. Other determinants of decreased cause-specific mortality were physical activity, body weight, and strictness of adherence to the life-style. The relationship between a vegetarian and fiber-rich diet and a decreased risk for colon cancer has been reported in many studies. In this study, the influence of other factors such as health-conscious behavior and a healthy lifestyle seem to indicate partly stronger effects than nutrition itself. This may explain the generally better health of moderate vegetarians.

PMID: 8172115

  Selected dietary risk factors and other environmental factors were studied in 119 adult patients (60 males and 59 females of the Cracow region) with acute leukaemia (91 acute myeloid leukaemia and 28 acute lymphoblastic leukaemia), by a case-control study method and logistic regression modelling of the risk of leukaemia. It was shown that the diet of patients with acute leukaemias before the onset of the disease differed qualitatively and quantitatively from that of healthy subjects of control groups. The risk of acute leukaemia was elevated in the subjects characterized by rare consumption of raw vegetables, frequent drinking of milk, frequent consumption of poultry, and drinking of soft water. Other environmental conditions connected with the dietary risk were: frequent viral infections, vaccination with the vaccinia virus, frequent use of aminophenazone, presence of fungi in the house, drinking of milk supplied from one's own cows, and frequent deaths of reared poultry.

PMID: 8461864

  Mammalian lignans such as enterolactone and enterodiol, which are produced in the colon from precursors in foods, have been suggested as playing a role in the cancer-protective effect of vegetarian diets. Despite this, very little is known regarding the amount that is produced from different food products. Therefore, the objective of this study was to determine the production of mammalian lignans from 68 common plant foods by using the technique of in vitro fermentation with human fecal microbiota, which simulates colonic fermentation. Results showed a wide range (21-67,541 microgram(s)/100 g sample) in the amount of lignans produced. On the average as a group, the oilseeds produced the highest amounts (20,461 +/- 12,685), followed by the dried seaweeds (900 +/- 247), whole legumes (562 +/- 211), cereal brans (486 +/- 90), legume hulls (371 +/- 52), whole grain cereals (359 +/- 81), vegetables (144 +/- 23), and fruits (84 +/- 22). The vegetables produced the second highest concentration of lignans (1,546 +/- 280) when the data were expressed on a moisture-free basis. Flaxseed flour and its defatted meal were the highest producers of lignans (mean 60,110 +/- 7,431). Lignan production with the in vitro method related well to the urinary lignan excretion observed in rats and humans. The data should be useful in the estimation of lignan production from a given diet and in the formulation of high-lignan-producing diet for the purpose of reducing the cancer risk.

PMID: 1656395

  The relationship between leukemia and occupation was investigated in a case-control study using death certificates of 5,147 men who died of leukemia (ICD-9 codes 204-208) and 51,470 who died of other causes in 16 U.S. states from 1985 to 1987. Of six occupational activities identified previously as potentially increasing the risk of leukemia, only petroleum refining and rubber manufacturing had excess deaths for all leukemias combined (odds ratios (ORs) = 1.3, 95% confidence intervals (CI) = 0.6-2.8 and 0.9-1.8, respectively). Meat workers and wood workers had elevated mortality from acute lymphocytic leukemia (OR = 2.2, 95% CI = 0.7-7.0 and OR = 1.3, 95% CI = 0.8-2.2, respectively). There was no leukemia excess among farmers or auto mechanics. A survey of 43 other occupational groups indicated a widespread excess of leukemia among white collar occupations, primarily managers and professionals, but none among blue collar workers. This pattern was most pronounced for men under 65 years of age, and existed for all leukemia subtypes and among both blacks and whites. Despite the lack of specific exposure information and other limitations of death certificate data, these results encourage further examination of occupational causes of leukemia.

PMID: 2035549

  Most studies of diet and colorectal cancer have considered nutrients and micronutrients, but the role of foods or food groups remains open to debate. To elucidate the issue, we examined data from a case-control study conducted between 1992 and 1997 in the Swiss canton of Vaud. Cases were 223 patients (142 men, 81 women) with incident, histologically confirmed colon (n= 119) or rectal (n= 104) cancer (median age 63 years), linked with the Cancer Registry of the Swiss Canton of Vaud, and controls were 491 subjects (211 men, 280 women, median age 58 years) admitted to the same university hospital for a wide spectrum of acute non-neoplastic conditions unrelated to long-term modifications of diet. Odds ratios (OR) were obtained after allowance for age, sex, education, smoking, alcohol, body mass index, physical activity and total energy intake. Significant associations were observed for refined grain (OR = 1.32 for an increase of one serving per day), and red meat (OR = 1.54), pork and processed meat (OR = 1.27), alcohol (OR = 1.28), and significant protections for whole grain (OR = 0.85), raw (OR = 0.85) and cooked vegetables (OR = 0.69), citrus (OR = 0.86) and other fruits (OR = 0.85), and for coffee (OR = 0.73). Garlic was also protective (OR = 0.32 for the highest tertile of intake). These findings in a central European population support the hypothesis that a diet rich in refined grains and red meat increases the risk of colorectal cancer; they, therefore, support the recommendation to substitute whole grains for refined grain, to limit meat intake, and to increase fruit and vegetable consumption.

PMID: 10098773

  BACKGROUND: Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma.
  METHODS: We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88 410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P<.05.
  RESULTS: Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend =.42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% CI = 1.1-4.4; P for trend =.002). Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend =.01). Higher intake of red meat cooked by broiling or barbecuing-but not by roasting, pan-frying, or boiling or stewing-was associated with an increase in risk that was not statistically significant.
  CONCLUSIONS: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma. These relationships and their potential mechanisms deserve further examination.

PMID: 10528026

  Prostate cancer is the most common malignancy in men in the United States, with substantially higher rates among American blacks than whites. We carried out a population-based case-control study in three geographic areas of the United States to evaluate the reasons for the racial disparity in incidence rates. A total of 932 men (449 black men and 483 white men) who had been newly diagnosed with pathologically confirmed prostate cancer and 1201 controls (543 black men and 658 white men) were interviewed in person to elicit information on potential risk factors. This report evaluates the impact of dietary factors, particularly the consumption of animal products and animal fat, on the risk of prostate cancer among blacks and whites in the United States. Increased consumption (grams/day) of foods high in animal fat was linked to prostate cancer (independent of intake of other calories) among American blacks [by quartile of intake, odds ratio (OR) = 1.0 (referent), 1.5, 2.1, and 2.0; Ptrend = 0.007], but not among American whites [by quartile of intake, OR = 1.0 (referent), 1.6, 1.5, and 1.1; Ptrend = 0.90]. However, risks for advanced prostate cancer were higher with greater intake of foods high in animal fat among blacks [by quartile of intake, OR = 1.0 (referent), 2.2, 4.2, and 3.1; Ptrend = 0.006] and whites [by quartile of intake, OR = 1.0 (referent), 2.2, 2.6, and 2.4; Ptrend = 0.02]. Increased intake of animal fat as a proportion of total caloric intake also showed positive but weaker associations with advanced prostate cancer among blacks (Ptrend = 0.13) and whites (Ptrend = 0.08). No clear associations were found with vitamin A, calcium, or specific lycopene-rich foods. The study linked greater consumption of fat from animal sources to increased risk for prostate cancer among American blacks and to advanced prostate cancer among American blacks and whites. A reduction of fat from animal sources in the diet could lead to decreased incidence and mortality rates for prostate cancer, particularly among American blacks.

PMID: 9950236

  OBJECTIVE: To analyze the relation between selected dietary indicators and the risk of uterine myomas.
  METHODS: We used data from a case-control study on risk factors for uterine myomas conducted in Italy between 1986 and 1997. Cases included 843 women with uterine myomas whose clinical diagnoses dated back no more than 2 years. Controls were 1557 women younger than age 55 who had not had hysterectomies and were admitted for acute nongynecologic, nonhormonal, nonneoplastic conditions.
  RESULTS: Women with uterine myomas reported more frequent consumption of beef, other red meat, and ham and less frequent consumption of green vegetables, fruit, and fish. The multivariate odds ratios in the upper tertile were 1.7 for beef and other red meat (95% confidence interval [CI] 1.4, 2.2), 1.3 for ham (95% CI 1.0, 1.6), 0.5 for green vegetables (95% CI 0.4, 0.6), and 0.8 for fruit consumption (95% CI 0.6, 1.0).
  CONCLUSION: Myoma is associated with beef and ham consumption, whereas high intake of green vegetables seems to have a protective effect.

PMID: 10472866

  The relation between selected indicator foods, alcohol and coffee intake, and the risk of pancreatic cancer was evaluated in a case-control study conducted between 1983 and 1992 in northern Italy on 362 patients with histologically confirmed, incident cancers of the pancreas, and 1,552 controls in hospital for acute, non-neoplastic diseases. Odds ratios (ORs) for subsequent tertiles of intake were computed after allowance for sociodemographic factors and tobacco smoking. Pancreatic cancer risk was directly associated with consumption of meat (OR for the highest frequency tertile = 1.43), liver (OR = 1.43) and ham and sausages (OR = 1.64), and inversely with consumption of fresh fruit (OR = 0.59), fish (OR = 0.65) and olive oil (OR = 0.58). No appreciable association was found with coffee (OR = 1.21) and alcohol consumption (OR = 1.20). A summary score was derived by summing the six related food items; compared to the lowest level, the OR was 2.7 for the highest quintile, and the population attributable risk was 36% (95% confidence interval, 15-57%), indicating the scope of diet for the prevention of this common neoplasm in the Italian population.

PMID: 9926293

  Production of reactive oxygen species in the lumen of the colon, a process that is influenced by nutritional factors, may be important in the etiology of colorectal cancer. Because research on humans in support of this hypothesis is lacking, the objective of this study was to measure the effect of different dietary compositions on the in vitro oxygen radical production in human feces. Over a period of 12 d, seven healthy subjects received a diet rich in fat (50%) and meat and poor in dietary fiber. After a period of 1 wk, they received a vegetarian diet poor in fat (20%) and rich in dietary fiber. At the end of each study period, feces were collected and analyzed for in vitro oxygen radical production with dimethylsulfoxide as the free radical scavenger. The mean hydroxyl radical production was 13 times greater in feces of subjects when they consumed the diet rich in fat [and meat] and poor in dietary fiber [52.7 +/- 29.5 micromol/(g feces x h)] than when they consumed the diet poor in fat and rich in dietary fiber [3.9 +/- 3.9 micromol/(g feces x h); P < 0.05]. This difference was associated with a 42% higher fecal iron concentration when they consumed the first diet (7.0 +/- 19.2 micromol/g feces) than when they consumed the second (4.9 +/- 1.9 micromol/g feces; P < 0.05). The results of this study confirm that diets high in fat and meat and low in fiber markedly increase the potential for hydroxyl radical formation in the feces, which in turn may contribute to an enhanced risk of colorectal cancer.

PMID: 9164990

  This investigation studied the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces and on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lacto-vegetarian diet, there was a significant decrease in mutagenic activity in urine and feces, beta-glucuronidase, beta-glucosidase, and sulphatase per gram feces wet weight. In contrast, the fecal mutagenic activity and the enzyme activities remained unchanged if expressed per daily output. However, the urinary mutagenic activity expressed as total daily output decreased. Part of the explanation for the decreased fecal mutagenic activity and the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content.

PMID: 9167043

  We reviewed the main results of colon cancer (CC) epidemiologic studies, according to data published in the 1973-1994 period, with a particular mention to dietary factors and to differences with Italian findings. Meat (mostly, red meat), animal fats and high energy intake not counterbalanced by sufficient physical activity seem to be the most consistent risk factors for CC. On the contrary, the vegetarian based diet seems to reduce the risk of CC. Although interestingly, the relevance to CC of other life-style and diet-related factors (alcohol intake, smoking habits, processing and cooking methods, occupation, drugs, personal medical and reproductive history) must be better defined and requests further investigations. More recently, genetic studies are clarifying the hereditary risk of CC. Several colon carcinogenesis hypotheses have been proposed, but general agreement on the most reliable is still lacking. Authors argue that in the next future, new acquirements could emerge from metabolic polymorphism studies, possibly reconciling the biological significance of individual susceptibility and environmental factors to CC incidence.

PMID: 9382427

  High red meat diets have been linked with risk of sporadic colorectal cancer; but their effects on mutations which occur in this cancer are unknown. G-->A transitions in K-ras occur in colorectal cancer and are characteristic of the effects of alkylating agents such as N-nitroso compounds (NOC). We studied the effect of red meat consumption on faecal NOC levels in eight male volunteers who consumed diets low or high in meat (60 or 600 g/day), as beef, lamb or pork, whilst living in a metabolic suite. Increased intake of red meat induced a significant (P<0.024) 3-fold increase from 40 + or - 7 to ab average of 113 + or - 25 microgram/day NOC, a range of exposure in faeces similar to that from tobacco-specific NOC in cigarette smoke. THe diets were isoenergetic and contained equal amounts of fat, but concentrations of heterocyclic amines were low. Faecal excretion of the promotor ammonia was significantly increased to 6.5 + or - 1.08 mmol/day. When the high red meat diets were supplemented with 20 g phytate-free wheat bran in six volunteers there was no reduction in NOC levels (mean 138 + or - 41 microgram/day NOC), but faecal weight increased. Higher starch and non-starch polysaccharide intakes reduced intraluminal cross-linking in microcapsules (r=-0.77) and reduced faecal pH (r=-0.64). In two volunteers there was no effect of 600 g white meat and fish on faecal NOC (mean low white meat diet 68 + or - 10 microgram/day, high white meat 56 + or -6 microgram/day nor on faecal nitrate, nitrite and iron. Faecal nitrite levels increased on changing from a white to red meat diet (mean high white meat diet 46 + or - 7 mg/day, high red meat diet mean 80 + or - 7 mg/day.) Increased endogenous production of NOC and precursors from increased red meat, but not white meat and fish, consumption may be relevant to the aetiology of colorectal cancer.

PMID: 863113

  Fecapentaenes are strong fecal mutagenic compounds presumably occurring in the majority of Western human individuals, and are possibly essential initiators of colon carcinogenesis. Dietary factors have been shown to influence colorectal cancer risk and to modulate both fecal mutagenicity and fecapentaene concentrations. Therefore, in this study, excretion of fecapentaenes is determined in humans consuming either vegetarian or omnivorous diets. The results show that the most predominant fecapentaene forms are excreted in higher concentrations by vegetarians. Consumption of cereal fiber, calcium and carotene as well as fecal concentrations of iso-lithocholic acid were found to correlate positively with excreted concentrations of one or more fecapentaene analogues. On average, 22% of excreted fecapentaene concentrations was found to be related to nutrient intake in stepwise regression models. Dietary calcium intake was found to be the most significant factor positively correlating with excreted fecapentaene concentrations. Intake of mono-unsaturated fatty acids or fiber from vegetables and fruit could be shown to correlate with fecapentaene excretion to a lesser degree. Despite high fecapentaene concentrations in fecal dichloromethane extracts, only 1 out of 20 samples revealed significant mutagenic activity in Salmonella typhimurium TA 100. Further, aqueous extracts of feces from omnivores appeared to be equally mutagenic as feces from vegetarians and contained non-detectable concentrations of fecapentaenes. It is concluded that dietary factors do affect excreted fecapentaene levels, but only to a relatively minor extent. Since vegetarians at low risk for colorectal cancer excrete higher concentrations of fecapentaenes, it could be hypothesized that relatively increased fecapentaene excretion in combination with antimutagenic compounds in feces represents colon cancer prevention.

PMID: 1540928

  This investigation studied the effects of a shift from a mixed diet to a lactovegetarian diet on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lactovegetarian diet, there was a significant decrease in beta-glucuronidase, beta-glucosidase, and sulphatase activities per gram feces wet weight (p less than 0.05, less than 0.05, and less than 0.001, respectively). In contrast, glucuronide and glucoside hydrolysis remained unchanged per gram dry weight, although sulphatase activity was still significantly lowered when expressed this way (p less than 0.01). However, the fecal excretion increased significantly (p less than 0.05). Part of the explanation for the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content. The higher water content was probably due to a higher fiber intake (p less than 0.001). Thus, the results in this paper indicate that a change from a mixed diet to a lactovegetarian diet leads to a decrease in certain enzyme activities proposed to be risk factors for colon cancer.

PMID: 2128119

  The study reports a series of case-referent studies based on the New Zealand Cancer Register and involving 19,904 male cancer patients aged 20 years or more at the time of registration during the period 1980-1984. For each cancer site, the registrations for the remaining sites formed the reference group. An increased risk for lung (OR 1.30, 95% CI 1.06-1.58) and laryngeal (OR 2.01, 95% CI 1.19-3.39) cancer was found among meatworkers. It was confined to men aged less than 65 years at registration. The risk for soft-tissue sarcoma was elevated (OR 1.90, 95% CI 0.90-4.02). The risk estimate for all types of leukemia was elevated moderately (OR 1.45, 95% CI 0.90-2.31), but cell type-specific analyses revealed a greater effect for acute myeloid leukemia (OR 2.12, 95% CI 1.09-4.12). This study adds to the evidence that employment as a meatworker is associated with increased risk for several forms of cancer.

PMID: 2922585

  Mortality among 5145 nonwhite men in a local meatcutters' union in Baltimore who were observed between July 1949 and December 1980, was compared with that of nonwhite men of the United States general population, through the estimation of standardized mortality ratios. The study population had potential for exposure to viruses that cause leukemia and lymphoma in cattle and chickens, and other harmful agents. Statistically significant standardized mortality ratios of 2.1 for lung cancer and 3.1 for cancer of the esophagus were observed among workers in abattoirs and meatpacking plants, respectively. The results obtained are consistent with findings for white male and female members of the same union, and with other published data.

PMID: 2918412

  South Asian immigrants to England and Wales have low mortality from colon cancer and high mortality from coronary heart disease compared with the general population. In a survey of a predominantly Gujarati population in northwest London, both vegetarians and nonvegetarians had similar total dietary fat intake to the native British population but higher dietary fiber intake. Total fecal bile acid and neutral animal sterol concentrations were lower in South Asians than in a native British comparison group. Sixty-two percent of South Asians excreted detectable quantities of free primary bile acids, which were not present in stools from native British subjects. The ratio of fecal coprostanol to total neutral animal sterols was also lower in South Asians. Low risk of colon cancer in this population may be related to reduced microbial activity in the bowel and low levels of tumor-promoting secondary bile acids.

PMID: 2750687

  To test the large number of hypotheses proposed as causes for childhood leukemia, a case control study was carried out on every child diagnosed for acute leukemia between 1.1.1977 and 12.31.1982, under the age of 15 and living in the region of Lyon (Rhone-Alpes and Saone-et-Loire). Some factors could not be confirmed, possibly in relation with the relatively small sample size (208 cases). Others were confirmed, especially the excess of incidence among 2 to 4 year old children and those belonging to higher socioeconomic groups. Two new factors were identified: the age of the father (over 40 years at child birth) and the profession of the father (manipulation of meat in the few years prior the diagnosis of leukemia in the child).

PMID: 3387182

  As part of a large-scale investigation of colorectal cancer (CRC) incidence, etiology, and survival, a case-control study was conducted to identify dietary factors associated with the risk of CRC. The study compared 715 cases with 727 age- and sex-matched community controls. A quantitative diet history, assessed to be the most representative of the previous 20 years, was obtained from each subject and analyzed for both food groups and nutrients. The combination of a high-fiber and high-vegetable intake was found to be protective against large bowel cancer. Cruciferous vegetable intake was also found, although with less certainty, to be protective. Dietary vitamin C was protective for estimated intakes greater than 230 mg/day. Dietary Beta-carotene had no separate association with the risk of CRC. Beef intake was a risk factor in males but not in females. Fat intake was a risk factor for both males and females. A low intake of milk drinks was a risk for both males and females. A high intake of pork and fish was protective. The use of vitamin supplements was highly protective. A risk score, which was calculated as the number of risk factors an individual has in his or her diet, showed an increasing monotonic relationship with risk of CRC. The effects of the dietary variables were similar for colon and rectal cancer and, with the exception of beef, were similar for males and females.

PMID: 3027675

  It has been reported that most human carcinomas result from exposure to the carcinogens present in certain foods, products of cigarette smoking and the general environment. A number of chemicals have already been isolated and tested for potential carcinogenesis in animals, and we report on the following aspects of chemical carcinogenesis. A series of new mutagenic heterocyclic amines have been isolated from pyrolysates of amino acids and proteins, and from cooked foods such as the charred parts of broiled fish and meat. Among these heterocyclic amines, nine compounds have been studied in long-term animal experiments, all of which were shown to cause carcinomas in mice. Some chemicals were also proved to be carcinogenic in rats. Because of their eating habits, people may simultaneously ingest mutagens and carcinogens, both of which have been found in certain cooked foods. Nitrosatable precursors of mutagens and tumor promoters have also been discovered in food--a finding of great importance in this particular context. Thus, it would appear that people are ingesting carcinogens, precursors of mutagens, tumor promoters, and tumor inhibitors, simultaneously. Commonly encountered human pathological conditions, such as viral and bacterial infections, non-infections inflammatory diseases, nutritional disorders, hormonal or homeostatic disturbances, gall and/or kidney stones, and benign proliferative disorders may be shown to be precursors for the development of future cancers. In most cases, however, the scientific evidence to support this theory has not been completely evaluated, but the existence of such pathological conditions should be taken into consideration whenever the development of a cancer is being studied. The division which at one time existed between basic cancer research and the clinical investigation of the disease has begun to disappear. The importance of clinical investigation and its use in the prevention of disease has been demonstrated, for example, in studies of adult human T-cell leukemia.

PMID: 3592686

  Mortality studies have indicated that workers in agriculture and forestry may be at increased risk of leukemia. Findings are reported from a New Zealand Cancer Registry-based case-control study involving 546 male leukemia patients registered during 1979-1983 and aged 20 years or more at time of registration. Controls were also males chosen from the Cancer Registry with four controls per case, matched on age and year of registration. The case group contained an excess of the occupational category involving agriculture and forestry (odds ratio (OR) = 1.24, 95% confidence interval (CI) = 0.95-1.61) with the greatest relative risk being for livestock farmers (OR = 3.00, 95% CI = 1.23-7.32). There was also an excess of electrical workers (OR = 1.72, 95% CI = 0.92-3.20). The agricultural excess was greatest in patients aged 65 years or more at time of registration (OR = 1.29, 95% CI = 0.94-1.78), particularly in patients with acute myeloid leukemia (OR = 1.55, 95% CI = 0.90-2.67) or acute monocytic leukemia OR = 10.38, 95% CI = 1.99-54.29), although the latter excess only involved five cases. Acute myeloid leukemia was also elevated in meat workers (OR = 2.51, 95% CI = 1.19-5.30).

PMID: 3740040

  A follow up study of 7261 white women from a meatcutters' union was conducted between July 1949 and December 1980. Proportional mortality ratio (PMR) and standardised mortality ratio (SMR) analyses, using the United States general population mortality rates, were conducted for the group as a whole and for subgroups defined according to the four main job categories in the meat industry, and a fifth category of workers from outside the industry but belonging to the same union (control group). At least a threefold risk of death was observed both for myeloid leukaemia and non-Hodgkin's lymphomas among workers in the meat department of retail food stores. No excess risk from these diseases was observed in the control group. SMRs of 4.56, 4.02, and 1.95, which were statistically significant, were observed for lung cancer among workers in chicken slaughtering plants, meatpacking plants, and retail food stores respectively. The lung cancer SMR for abattoir workers was 1.41 (not significant) and 1.11 for workers in non-meat companies. The role of potentially harmful exposures within the industry in the occurrence of these excesses is discussed.

PMID: 3756110

  Because of potential significance of fecal mutagens in the pathogenesis of colon cancer, the dietary pattern and fecal mutagens of 3 populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area (non-Seventh-Day Adventists), a low-risk population of vegetarian Seventh-Day Adventists in New York Metropolitan area and a low-risk population in rural Kuopio, Finland were studied. The average daily intake of protein was the same in the 3 groups, but the sources were different, a greater portion coming from meat in the New York non-Seventh-Day Adventists and from vegetables in Seventh-Day Adventists. The intake of fat was lower in Seventh-Day Adventists and higher in Kuopio and in New York non-Seventh-Day Adventists. The intake of dietary fiber was high in Kuopio compared to other groups. Fecal samples collected for 2 days were freeze-dried extracted with peroxide-free diethyl ether, partially purified on a silica-gel column and assayed for mutagenicity using the Salmonella/mammalian microsome mutagenicity test. The mutagenic activity was observed with Salmonella typhimurium tester strain TA98 without microsomal activation and with TA100 with and without microsomal activation in high-risk subjects from New York consuming a high-fat, high-meat diet. The incidence of fecal mutagen activity was higher in volunteers from New York consuming a high-fat, high-meat diet compared to low-risk rural Kuopio population. None of the vegetarian Seventh-Day Adventists showed any mutagenic activity.

PMID: 6256623

  Although there have recently been reports in the literature indicating that vegetarian-type diets are protective against the development of human colon cancer, this is still far from clear. It was also recently indicated that the concentration of acidic lipids in the aqueous phase of stool constitutes a risk factor for the development of colon cancer. Thus, we examined the effect of a change from a mixed to a lactovegetarian diet on this fecal variable. The dietary change caused a decrease in the total concentration of soluble fecal fatty acids (4310 +/- 3020 to 1080 +/- 1040 mumol/L, p less than 0.05) and deoxycholic acid (125 +/- 42 to 73 +/- 35 mumol/L, p less than 0.05). However, there was no change in either the total bile acid concentration in (164 +/- 54 to 107 +/- 41 mumol/L) or the cellular toxicity of (0.94 +/- 0.55 to 1.60 +/- 0.63 mumol/L, relative survival) the aqueous phase of stool. Thus, the consumption of a lactovegetarian diet may reduce certain risk factors of potential significance in colon carcinogenesis.

PMID: 2554715

  Using repair-proficient and repair-deficient strains of E. coli, we investigated the application of a liquid incubation assay to measure the DNA-damaging activity of ethanol-soluble fecal extracts. This method appears to be suitable for the study of a wide range of sample types. It was used to measure the DNA-modifying activity of ethanol-soluble fecal extracts from a group of European colorectal cancer patients. Data were compared with those from Europeans of similar age and sex distribution who did not have bowel cancer. We also studied groups of Maoris, Samoans, and European Seventh-Day Adventists who followed an ovo-lacto vegetarian diet. There are significant levels of DNA-modifying materials in the feces of many Europeans on a mixed diet, regardless of whether or not they have cancer. The number of positive samples was less in the Polynesian groups, and there were no samples that could be unequivocally scored as positive in the Seventh-Day Adventist groups. We conclude that diet can significantly reduce the level of ethanol-soluble mutagens, at least in New Zealand Europeans. The data may provide an explanation for the reduced incidence of bowel cancer in Seventh-Day Adventist groups.

PMID: 3906579

  Cholesterol and its metabolites, together with bile acids, are implicated as risk factors in the genesis and progression of colon cancer. This study was designed to determine differences in the neutral sterol composition of stools from four different population groups differing in their dietary habits as well as in their expected rates for colon cancer. Four study groups consisting of 18 Seventh-day Adventist (SDA) pure vegetarians, 50 SDA lacto-ovo vegetarians, 50 SDA nonvegetarians, and 50 general population nonvegetarians were selected from the greater Los Angeles Basin area. Three-day composite stool samples were lyophilized and then analyzed for their neutral sterol composition. Cholesterol excretion values consistently showed an age-dependent peak in 46- to 50-yr age group for the total population, SDA lacto-ovo vegetarian and SDA-nonvegetarian subgroups being the principal contributors to this age-dependent phenomenon. The SDA pure vegetarians exhibited the lowest fecal concentrations and daily excretion of cholesterol as expected since their intake of dietary cholesterol is insignificant. Among the other SDA, regardless of whether they are lacto-ovo vegetarians or nonvegetarians, their cholesterol excretion patterns were similar but higher than in the nonvegetarians from the general population. Since dietary intakes of cholesterol are not significantly different among the two nonvegetarian groups, the differences in excretion values are attributable to differences in colonic metabolism. The ratio of cholesterol/cholesterol metabolites showed generally lower values among nonvegetarians compared to the matched group of lacto-ovo vegetarians. The observation was made that fecal cholesterol and its metabolites tend to be higher among nonvegetarians compared to those in the corresponding vegetarian groups.

PMID: 6435444

  Fecal, urinary, and plasma estrogens and plasma androgens were studied in healthy pre- and postmenopausal vegetarian and omnivorous women. Dietary histories of the subjects revealed that omnivores consumed a higher percentage of total protein and fat from animal sources. The total 72-hr fecal excretion as measured by dry weight was higher for vegetarians. Preliminary results indicate that vegetarian women excrete 2 to 3 times more estrogens in feces than do omnivores and that omnivores have about 50% higher mean plasma level of unconjugated estrone and estradiol than vegetarians. Estriol-3-glucuronide, a compound that is formed upon reabsorption of free estriol from the intestine, is found in lower concentrations in the urine of vegetarians. These data suggest that in vegetarians a greater amount of the biliary estrogens escape reabsorption and are excreted with the feces. The differences in estrogen metabolism may explain the lower incidence of breast cancer in vegetarian women.

PMID: 7260944

  Mutagens in water extracts from feces of persons in 3 different diet groups were measured with the fluctuation test for weak mutagens using Salmonella typhimurium TA100 and TA98 as tester strains. The 3 diet groups were ovo-lacto vegetarians (N = 6), strict vegetarians (N = 11) and non-vegetarians (N = 12). All subjects were from the urban area of Vancouver, British Columbia, Canada. On TA100 ovo-lacto vegetarians and strict vegetarians had significantly lower levels of fecal mutagens than non-vegetarians (P less than or equal to 0.025 and P less than 0.010, resp.). The same pattern, although less significant, was obtained with TA98. Correlation studies between mutagenicity on TA100 and TA98 and between the pH of the fecal homogenate and mutagenicity indicate the presence of 2 or more major fecal mutagens.

PMID: 7010141

  Because of potential significance of fecal mutagens in the pathogenesis of colon cancer, the dietary pattern and fecal mutagens of 3 populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area (non-Seventh-Day Adventists), a low-risk population of vegetarian Seventh-Day Adventists in New York Metropolitan area and a low-risk population in rural Kuopio, Finland were studied. The average daily intake of protein was the same in the 3 groups, but the sources were different, a greater portion coming from meat in the New York non-Seventh-Day Adventists and from vegetables in Seventh-Day Adventists. The intake of fat was lower in Seventh-Day Adventists and higher in Kuopio and in New York non-Seventh-Day Adventists. The intake of dietary fiber was high in Kuopio compared to other groups. Fecal samples collected for 2 days were freeze-dried extracted with peroxide-free diethyl ether, partially purified on a silica-gel column and assayed for mutagenicity using the Salmonella/mammalian microsome mutagenicity test. The mutagenic activity was observed with Salmonella typhimurium tester strain TA98 without microsomal activation and with TA100 with and without microsomal activation in high-risk subjects from New York consuming a high-fat, high-meat diet. The incidence of fecal mutagen activity was higher in volunteers from New York consuming a high-fat, high-meat diet compared to low-risk rural Kuopio population. None of the vegetarian Seventh-Day Adventists showed any mutagenic activity.

PMID: 6256623