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Original Contribution |

Meat Consumption and Risk of Colorectal Cancer FREE

Ann Chao, PhD; Michael J. Thun, MD, MS; Cari J. Connell, MPH; Marjorie L. McCullough, ScD; Eric J. Jacobs, PhD; W. Dana Flanders, MD, ScD; Carmen Rodriguez, MD, MPH; Rashmi Sinha, PhD; Eugenia E. Calle, PhD
[+] Author Affiliations

Author Affiliations: Epidemiology and Surveillance Research, American Cancer Society (Drs Chao, Thun, McCullough, Jacobs, Flanders, Rodriguez, and Calle, and Ms Connell), and Department of Epidemiology, Rollins School of Public Health, Emory University (Dr Flanders), Atlanta, Ga; and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Md (Dr Sinha).

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JAMA. 2005;293(2):172-182. doi:10.1001/jama.293.2.172.
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Context Consumption of red and processed meat has been associated with colorectal cancer in many but not all epidemiological studies; few studies have examined risk in relation to long-term meat intake or the association of meat with rectal cancer.

Objective To examine the relationship between recent and long-term meat consumption and the risk of incident colon and rectal cancer.

Design, Setting, and Participants A cohort of 148 610 adults aged 50 to 74 years (median, 63 years), residing in 21 states with population-based cancer registries, who provided information on meat consumption in 1982 and again in 1992/1993 when enrolled in the Cancer Prevention Study II (CPS II) Nutrition Cohort. Follow-up from time of enrollment in 1992/1993 through August 31, 2001, identified 1667 incident colorectal cancers. Participants contributed person-years at risk until death or a diagnosis of colon or rectal cancer.

Main Outcome Measure Incidence rate ratio (RR) of colon and rectal cancer.

Results High intake of red and processed meat reported in 1992/1993 was associated with higher risk of colon cancer after adjusting for age and energy intake but not after further adjustment for body mass index, cigarette smoking, and other covariates. When long-term consumption was considered, persons in the highest tertile of consumption in both 1982 and 1992/1993 had higher risk of distal colon cancer associated with processed meat (RR, 1.50; 95% confidence interval [CI], 1.04-2.17), and ratio of red meat to poultry and fish (RR, 1.53; 95% CI, 1.08-2.18) relative to those persons in the lowest tertile at both time points. Long-term consumption of poultry and fish was inversely associated with risk of both proximal and distal colon cancer. High consumption of red meat reported in 1992/1993 was associated with higher risk of rectal cancer (RR, 1.71; 95% CI, 1.15-2.52; P = .007 for trend), as was high consumption reported in both 1982 and 1992/1993 (RR, 1.43; 95% CI, 1.00-2.05).

Conclusions Our results demonstrate the potential value of examining long-term meat consumption in assessing cancer risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.

Meat consumption has been associated with colorectal neoplasia in the epidemiological literature, but the strength of the association and types of meat involved have not been consistent. Few studies have evaluated long-term meat consumption or the relationship between meat consumption and the risk of rectal cancer. Studies of red meat consumption and colorectal adenoma have reported odds ratios in the range of 1.2 to 1.3.13 Case-control studies425 of colorectal cancer conducted in the United States and Europe have generally reported increased risk associated with red or processed meat intake in analyses of men,49,13,14 and men and women combined,1012,1525 but not in analyses that included only women.59,13 Case-control studies2632 of colorectal cancer among Asians in the United States or Asia have more consistently reported a positive association with red, processed, or total meats.

Five3337 of 103342 US prospective studies of colorectal cancer reported positive associations with red or processed meat intake, although some associations3537 did not reach statistical significance. European prospective studies4349 have generally reported no association with fresh or total meat but positive associations with cured or processed meat,43,45,46 sausages,47 or smoked/salted fish.45 High consumption of poultry or fish has been inconsistently associated with higher36,37,46 or lower34,40,41,47,49 risk of colorectal cancer; some studies have found no association.33,39,42,43,45,48 Only 2 prospective studies38,49 have reported on rectal cancer in relation to meat consumption. The results were conflicting but were limited by the small number of cases.

A meta-analysis50 of case-control and prospective studies estimated the mean relative risk comparing the highest to lowest categories of meat consumption to be 1.35 (95% confidence interval [CI], 1.21-1.51) for red meat and 1.31 (95% CI, 1.13-1.51) for processed meat and colorectal cancer. A review of prospective studies51 concluded that a daily increment of 100 g of red or total meat consumption was associated with a 12% to 17% higher risk of colorectal cancer, and that an increment of 25 g of processed meat was associated with a 49% higher risk. Not all risk estimates included in these review articles were adjusted for potential confounders beyond age and energy intake, so residual confounding may influence the summary risk estimates.

Clarifying the role of meat consumption in colorectal carcinogenesis is important. Meat is an integral component of diet in the United States and many other countries in which colorectal cancer is common. Per capita annual consumption of beef has increased in the United States since 1993, reversing a previous decrease since 1976. Poultry consumption has surpassed beef consumption since the late 1980s.52,53

An earlier analysis of the Cancer Prevention Study II (CPS II) Mortality Cohort, based on deaths from colorectal cancer from 1982 to August 1988, found no association between colorectal cancer mortality and high consumption of red meat, but suggested lower risk associated with higher intake of chicken and fish in women.41 We examined the relationship between meat consumption and incident colon and rectal cancers among 148 610 men and women enrolled in the CPS II Nutrition Cohort in 1992/1993.

Study Population

The CPS II Nutrition Cohort has been described in detail elsewhere.54 Briefly, the CPS II Nutrition Cohort comprised 86 404 men and 97 786 women who completed a mailed questionnaire in 1992/1993 and were followed up for cancer incidence and mortality. This cohort is a subset of the CPS II Mortality Cohort in which 1.2 million US adults from all 50 states, Puerto Rico, and the District of Columbia have been followed up for cancer mortality since 1982.54 In the CPS II Mortality Cohort, participants completed a self-administered questionnaire in 1982 with information on diet, exercise, medical history, and other lifestyle habits. Race was determined on this 1982 questionnaire by multiple choice (white, black, Hispanic, Oriental, and other). Enrollment in the CPS II Nutrition Cohort was limited to men and women aged 50 to 74 years, residing in 21 states with population-based cancer registries that demonstrated at least 90% ascertainment of incident cancers by 1990. The median age at the CPS II Nutrition Cohort enrollment was 63 years.

The 1992/1993 CPS II Nutrition Cohort questionnaire obtained information on diet, physical activity, medical history, and other lifestyle habits. This cohort was recontacted at 2-year intervals between 1997 and 2003 with self-administered questionnaires to update information on newly diagnosed cancers, medical history, and lifestyle factors. Reported cancer diagnoses through 2001 have been verified by clinical information obtained from medical records or linkage with state cancer registries. An earlier study linking CPS II Nutrition Cohort participants to state cancer registries demonstrated that self-report of any cancer could identify incident cancers with a sensitivity of 93%.55 Mortality follow-up of the entire CPS II Nutrition Cohort54 is ongoing through automated linkage with the National Death Index. Cohort participants on average report higher educational attainment and more behaviors suggesting health consciousness than the general US population.54 Participants were informed of data linkage activities on each mailed questionnaire and provided written consent by returning the completed questionnaire. All aspects of the CPS II study protocol were approved by the Emory University Institutional Review Board.

This analysis was based on 1667 incident cases of colon or rectal cancer diagnosed from the time of enrollment in 1992/1993 through August 31, 2001. Participants contributed person-years at risk until death or a diagnosis of colon or rectal cancer. Excluded from the analysis were persons who were not known to be deceased but failed to respond to the 1997, 1999, and 2001 questionnaires (3.7%); reported a colon or rectal cancer not verified by pathology report or death certificate (0.3%); reported at baseline a personal history of colon or rectal cancer (1.5%); reported uninterpretable or missing data on meat consumption in 1982 (4.7%); completed less than 85% of the food section of the 1992/1993 questionnaire; or reported implausibly high or low energy intake (9.1%). After exclusions, the analytic cohort included 69 664 men and 78 946 women, representing 81% of the CPS II Nutrition Cohort.

Incident Colon and Rectal Cancer

A total of 1197 incident cancers of the colon (International Classification of Diseases codes: C18.0, C18.2-C18.9)56,57 and 470 cancers of the rectosigmoid junction (C19.0)56,57 or rectum (C20.9)56,57 were identified. Of these, 665 colon and 291 rectal cancers were diagnosed in men, and 532 colon and 179 rectal cancers in women. A total of 1335 (80%) of 1667 colorectal cancers were self-reported on the 1997, 1999, or 2001 questionnaires and subsequently verified by medical record abstraction or linkage with state cancer registries; another 43 (3%) were identified while verifying a different reported cancer; and 289 (17%) were identified as interval deaths, defined as persons who died with colon or rectal cancer recorded on death certificate but not reported on the questionnaire. Linkage with state cancer registries confirmed the diagnosis of colon or rectal cancer in 74% of interval deaths. Subsite-specific analyses were conducted on 667 proximal (cecum to splenic flexure) and 408 distal (descending to sigmoid colon) colon cancers, excluding those with overlapping or unspecified site codes. We also present the results from analyses of 470 cancers of the rectosigmoid and rectum combined but not from separate analyses of the rectosigmoid junction (214 cases) or rectum (246 cases). The remaining 10 cases were unspecified (not able to distinguish as rectum or rectosigmoid junction).

Meat Consumption

Dietary assessment in 1992/1993 was based on a 68-item modified Block58 food-frequency questionnaire (FFQ); nutrient values were estimated using the Dietary Analysis System version 3.8a.59 Participants were asked to report their usual eating habits during the past year, including average frequency and serving size (small, medium, or large) of each food and beverage listed. Consumption of each meat item in grams per week was estimated by taking the product of average frequency per week, number of grams in a medium serving, and serving size (0.5 for small, 1.0 for medium, and 1.5 for large). Intake of red meat, poultry and fish, and processed meat (g/wk) was computed by summing across meat items that contributed to each meat group and categorizing by quintile. The lowest quintile of intake served as the referent group for analyses.

We considered red meat to include the following individual or grouped items on the questionnaire: bacon; sausage; hamburgers, cheeseburgers, meatloaf, or casserole with ground beef; beef (steaks, roasts, etc, including sandwiches); beef stew, or pot pie with carrots or other vegetables; liver, including chicken livers; pork, including chops, roast; hot dogs; and ham, bologna, salami, or lunchmeat. Food items classified as poultry and fish included chicken or turkey (roasted, stewed, broiled, ground, including sandwiches); fried chicken; fried fish or fish sandwich; tuna, tuna salad, tuna casserole; and other fish (broiled or baked). We considered processed meat to include bacon; sausage; hot dogs; and ham, bologna, salami, or lunchmeat. We computed the ratio of red meat-to-poultry and fish by dividing red meat intake by intake of poultry and fish (g/wk); individuals were assigned to the lowest or highest quintile when either value was 0. An additional question, “How often did you eat beef, pork, or lamb as a main dish, eg, steak, roast ham, etc (4-6 ounces)?” was included for comparison with other studies that included this question. Participants were also asked, “When you eat red meat such as beef, pork, or lamb, how well done is it cooked?” with the following possible responses on the questionnaire, “well-done, medium well done, medium rare, rare, and don’t eat red meat.”

The 1992/1993 FFQ was validated among 441 Nutrition Cohort members who completed four 24-hour dietary recall interviews and a repeat FFQ.60 For red meat, the correlation coefficient between the FFQ and dietary recall interview was 0.55 among men and 0.78 in women; between the initial FFQ and the repeat FFQ, the correlation coefficient was 0.81 in men and 0.78 in women.

The 1982 questionnaire asked participants to report the average number of days per week they ate each of the 11 meat items. Intake frequencies of red meat, poultry and fish, and processed meat were computed by summing the number of days per week across individual meat items that contributed to each meat group, and categorizing into quintiles. Foods categorized as red meat were beef, pork, ham, liver, smoked meats, frankfurters/sausage, fried bacon, and fried hamburger; poultry and fish included chicken, fish, and fried chicken/fish; and processed meats included ham, smoked meats, frankfurters/sausage, and fried bacon. Turkey was not included on the 1982 questionnaire but was included on the 1992/1993 questionnaire.

We examined long-term meat consumption by considering consumption reported in 1982 and in 1992/1993. Consumption at each time point was categorized into tertiles (low, moderate, high) and participants were classified as low intake in 1982 and 1992/1993 (referent group), high intake in 1982 and 1992/1993, and all other combinations of intake over time.

Statistical Analysis

Colon and rectal cancer incidence rate ratios (RRs) and 95% CIs by meat intake were estimated using Cox proportional hazards regression modeling. P values for linear trend were estimated by modeling meat intake (g/wk) using the median value within quintiles; these results were similar when modeled as continuous variables. This study was observational, not randomized, so P values were interpreted as approximate.61 To obtain P values and confidence limits, we treated the disease outcome as though it were a random variable that changed over time. Potential confounders were chosen based on a priori considerations and on the observed association with colon or rectal cancer and meat intake.

For each meat variable, we constructed 3 models stratified by single year of age, controlling for other covariates. Model 1 also included total energy (continuous); model 2 included total energy, education (some high school, high school graduate, some college or trade school, college graduate or postgraduate work, or unknown), body mass index calculated as weight in kilograms divided by the square of height in meters in 1992/1993 (<18.5, 18.5-24.9, 25.0-29.9, 30.0-39.9, ≥40.0, or unknown), cigarette smoking in 1992/1993 (never, former, current, ever smoker not specified, or unknown), recreational physical activity in 1992/1993 (none, hours per week of walking, or walking plus other activities), multivitamin use in 1982 (none, current user, or unknown), aspirin use in 1982 and in 1992 (nonuser in 1982 and 1992, ≥15 days per month in 1982 and 1992, <15 days per month in 1982 or 1992, or unknown at either time point), intake of wine (none, any), beer (none, any), and liquor (none, any), and hormone therapy use in 1992/1993 among women (nonuser, former user, current user, ever user not specified, or unknown). Model 3 included all covariates in model 2 plus intake of fruits in 1992/1993 (quintiles), vegetables in 1982 (quintiles), and high-fiber grain foods in 1982 (quintiles). Models of men and women combined also included a term for sex. Family history of colorectal cancer reported in 1982 was examined and excluded as a potential confounder; no information on family history of colorectal cancer was available in 1992/1993. Results of models including age and energy were similar to those from models including only age or age plus energy in quintiles. In a subanalysis of meat consumption reported in 1992/1993, we examined quintiles of energy-adjusted intake of red meat, poultry and fish, and processed meat based on the residual method.62 We also examined how the association with each type of meat was affected when controlling for other types of meat; no substantial difference was observed in these analyses (results not shown).

We tested the proportional hazard assumption for each meat intake variable in relation to colon or rectal cancer using the likelihood ratio test, comparing models with and without product terms for meat consumption (quintiles) and follow-up time (years). We evaluated effect modification of the RR for colon and rectal cancer in relation to meat consumption by other covariates using the likelihood ratio test comparing models with and without interaction terms. The Wald statistic was used to test for homogeneity of the RR for proximal and distal colon cancers.63 All P values were 2-sided and considered significant at P<.05. All analyses were conducted using SAS version 9.0 (SAS Institute Inc, Cary, NC).

Participant Characteristics by Meat Consumption

Men and women reported a wide range in consumption of red and processed meat in 1992/1993. A 10-fold difference was observed between the lowest and highest quintiles of red meat in men and a 17-fold difference in women (Table 1). Men reported greater consumption of red and processed meat than did women; median intake was 427 g/wk and 274 g/wk for red meat among men and women, respectively, and 95 g/wk and 43 g/wk for processed meat, respectively. There was little variation in the consumption of poultry and fish by quintiles of red meat intake. Men also reported substantially higher intake of red and processed meats in 1982 than did women (data not shown). Approximately half of the men and women in the top tertile for consumption of red or processed meat in 1982 were also in the highest tertile in 1992/1993 (data not shown). The absolute levels of meat consumption in 1982 could not be compared with consumption in 1992/1993 due to differences in the questionnaires.

Table Graphic Jump LocationTable 1. Selected Characteristics of Study Participants by Red Meat Consumption in the Year Before Study Enrollment*

Men and women who reported higher intake of red meat in 1992/1993 (Table 1) were more likely to report lower educational attainment, no recreational physical activity, higher body mass index, current cigarette smoking, beer and liquor drinking, higher total daily energy intake, low fruit intake in 1992/1993, and little or no intake of vegetables or high-fiber grain foods in 1982 compared with those with lower red meat intake. Men and women who reported lower red meat intake tended to report multivitamin use in 1982, wine drinking, and (in women) use of hormone therapy in 1992/1993.

Meat Consumption and Colon Cancer Incidence

Table 2 shows the relationship between colon cancer incidence and meat consumption as reported in 1992/1993. Higher intake of red and processed meat was associated with higher colon cancer risk in men and women in models that adjusted only for age and energy intake (model 1). However, the positive associations were attenuated in analyses (model 2) that further adjusted for nondietary factors, including education, body mass index, cigarette smoking, recreational physical activity, use of multivitamins or aspirin, and (in women) use of hormone therapy. Further adjustment for dietary factors (model 3) had little effect on the RR estimates. No association was observed between colon cancer incidence and consumption frequency of beef, pork, or lamb as a main dish, or with reported preference for red meat doneness (data not shown).

Table Graphic Jump LocationTable 2. Meat Consumption Reported by Men and Women in 1992/1993 and Colon Cancer Cases by Quintile for All 3 Models*

Higher consumption of poultry and fish was inversely associated with colon cancer risk in women but not men (Table 2). Further adjustment for additional covariates other than energy attenuated the association. Among women, the inverse relationship remained statistically significant (P = .03 for trend). The positive association between colon cancer risk and ratio of red meat-to-poultry and fish intake was also stronger in women than men. The trend test for the ratio of red meat-to-poultry and fish intake was statistically significant in men, women, and both sexes combined. The inverse, marginally significant, association between high consumption of poultry and fish and colon cancer risk in men and women remained unchanged when adjusting simultaneously for red meat (data not shown).

Proximal and Distal Colon Cancer, and Rectal Cancer

Table 3 shows the relationship between meat consumption reported in 1992/1993 and incident colon cancer by subsite and rectal cancer in men and women combined. After covariate adjustment, no consistent association was observed between consumption of red meat, poultry and fish, or processed meat as reported at a single time point and cancer of either subsite of the colon. Men and women in the second to fifth quintiles of red meat intake had higher risk of rectal cancer compared with those in the lowest quintile, particularly those individuals in the highest quintile (RR, 1.71; 95% CI, 1.15-2.52; P = .007 for trend). This association was observed primarily with cancers of the rectosigmoid junction (RR, 2.40; 95% CI, 1.30-4.43) with risk increasing significantly with the amount of red meat consumed (P = .002 for trend). No significant association was observed between red meat consumption and cancers of the rectum (data not shown). No clear association was observed between rectal cancer risk and other measures of meat consumption reported in 1992/1993.

Table Graphic Jump LocationTable 3. Meat Consumption of Men and Women Combined Reported in 1992/1993 and Proximal Colon, Distal Colon, and Rectal Cancer Cases by Quintile*
Energy-Adjusted Meat Intake

Analyses using energy-adjusted meat intake reported in 1992/1993 yielded results similar to those using meat intake (g/wk) with few exceptions. Compared with risk estimates derived from nonenergy-adjusted meat intake, the association between colon cancer and consumption of processed meat (RR, 1.35; 95% CI, 1.04-1.77; highest to lowest quintile, P = .02 for trend) became stronger in men, although the association between rectal cancer and red meat intake (RR, 1.31; 95% CI, 0.96-1.79; P = .03 for trend) was attenuated in men and women combined. Other risk estimates for red meat, poultry and fish, and processed meat remained unchanged.

Long-term Meat Consumption

Table 4 presents multivariate-adjusted RRs for colon cancer by subsite and rectal cancer among persons who were in the highest tertile of meat consumption in both 1982 and 1992/1993 compared with those in the lowest tertile at both time points. Prolonged high consumption of red meat was associated with a statistically nonsignificant increased risk of distal colon cancer (RR, 1.29; 95% CI, 0.88-1.89). The most consistent associations were observed between distal colon cancer and prolonged high intake of processed meat (RR, 1.50; 95% CI, 1.04-2.17), and ratio of red meat to poultry and fish (RR, 1.53; 95% CI, 1.08-2.18) compared with persons with prolonged low intake. These associations were not observed with cancer of the proximal colon. The association between distal colon cancer and consumption of processed meat was stronger in analyses based on long-term consumption than on that reported only in 1982 (data not shown). Long-term high intake of poultry and fish was marginally associated with lower risk of proximal (RR, 0.77; 95% CI, 0.59-1.02) and distal (RR, 0.70; 95% CI, 0.50-0.99) colon cancer.

Table Graphic Jump LocationTable 4. Meat Consumption and Meat Intake of Men and Women Reported in 1982 and 1992/1993, and Cases of Proximal Colon, Distal Colon, and Rectal Cancer*

Red meat consumption was marginally associated with higher risk of rectal cancer (RR, 1.43; 95% CI, 1.00-2.05); this association was somewhat stronger for cancers of the rectosigmoid junction (RR, 1.75; 95% CI, 1.04-2.96) than for cancer of the rectum (RR, 1.31; 95% CI, 0.79-2.15). The relationship between long-term consumption of red meat, poultry and fish, and risk of colon or rectal cancer remained unchanged when all were included in the same model (data not shown).

Effect Modification

No statistically significant interaction was observed between meat consumption and other known risk factors for colon or rectal cancer on a multiplicative scale.

The association between processed meat consumption and colon cancer risk was independent of other covariates only when intake was measured at 2 time points during a 10-year interval. Moreover, the association was observed consistently only for cancers of the distal colon. Prolonged high consumption of red meat was associated with higher risk of rectal cancer, particularly cancers of the rectosigmoid junction. Prolonged high consumption of poultry and fish was marginally associated with lower risk of proximal and distal colon cancer but not rectal cancer.

A strength of our study was the ability to control for several factors known to influence colon cancer risk. Inadequate control for potential confounding may partly explain the inconsistently observed positive associations between red meat and colon cancer risk in other studies, since some positive articles included in the quantitative reviews50,51 have adjusted for only age and energy. In our analyses, the association between colon cancer risk and high intake of red (RR, 1.41; 95% CI, 1.12-1.78) and processed meat (RR, 1.33; 95% CI, 1.08-1.64) measured at a single time point is consistent with meta-analysis results,50 adjusting for age and energy intake. However, the association was substantially attenuated with further adjustment for educational attainment, cigarette smoking, physical activity, and other lifestyle factors associated with red meat intake.

To our knowledge, no study has addressed the relationship between long-term meat consumption and risk of colon and rectal cancer. The association with distal colon cancer was stronger among persons who reported greater consumption of processed meat at 2 time points during a 10-year interval, as was the risk of cancer of the rectosigmoid junction among those persons who consistently reported high red meat intake. It is possible that true high consumers of red or processed meat were better defined with less measurement error when assessed twice during a 10-year period. It is also plausible that long-term high consumption of red and processed meat may be more strongly associated with colorectal carcinogenesis than short-term or sporadic consumption of meat. Certain components of red meat may affect both early and late stages in the development of neoplasia. Animal studies show that diets high in red meat tend to affect the early aberrant crypt stage of carcinogenesis.64 To our knowledge, no study has evaluated the importance of continued high exposure to red meat in animal models.

The higher risk associated with prolonged consumption of red meat but not poultry and fish is consistent with other epidemiological studies.33,34,38,40 The cytotoxic effect of dietary heme has been proposed as a potential mechanism by which red meat increases colorectal cancer risk because of higher heme content in red meat compared with poultry and fish.65,66 Heme damages the colonic mucosa and stimulates epithelial proliferation in animal studies.66 Both ingestion of red meat and heme iron supplementation have been shown to increase fecal concentrations of N-nitroso compounds65 and DNA-adducts in human colonocytes.67,68

We found that consistently high consumption of processed meat was associated with increased risk of distal colon cancer. Results of prospective studies of colorectal cancer and processed meat have been more consistently positive in Europe43,45,47 than in the United States.33,34,39,40,42 Processed meat includes foods preserved by salting, smoking, or the addition of nitrites or nitrates, and high consumption of these foods can increase exposure to nitrosamines and their precursors. The amount of these substances in processed meat likely varied by region and over time but we had no information to assess the impact of these differences in our study results.

Several prospective studies have reported an inverse association between colon cancer risk and prolonged high consumption of poultry and fish.34,40,41,47,49 However, other studies have found either no association33,39,42,43,45,48 or increased risk36,37,46 associated with poultry and fish consumption. The lower risk associated with high consumption of poultry and fish or a low ratio of red meat-to-poultry and fish could be attributed to a displacement of red meat in the diet, but in our study high consumption of poultry and fish remained independently associated with lower risk of colon cancer even when controlling for red meat intake. It is also possible that poultry and fish contain factors that may protect against colon cancer. Poultry contains small amounts of nutrients such as selenium and calcium that have been associated with lower risk of colorectal neoplasia,6971 but it is a relatively minor source of these nutrients. Fish is a primary source of omega-3 fatty acids and high intake of fish or fish oil has been inversely associated with colorectal cancer risk in some epidemiological studies.40,47,72 In experimental studies, omega-3 fatty acids have been shown to inhibit tumor growth and to modulate the expression of proinflammatory genes.73,74 However, the poultry and fish consumed by CPS II Nutrition Cohort participants consisted mostly of chicken.

Our findings add to the limited prospective data38,49,75 on meat consumption in relation to rectal cancer. Consumption of red meat, as reported in 1992/1993, was more strongly associated with rectal than colon cancer in our study, as has been reported in some4,5,20,21 but not all17,18,23,24,28,29 case-control studies. One recent case-control study found no association between rectal cancer and red meat, poultry and fish, or processed meat consumption but reported increased risk associated with greater doneness of red meat among men.76 In our study, the positive association and significant dose-response relationship was observed mostly with tumors of the rectosigmoid junction rather than the rectum. Taken together with the higher risk of cancer observed in the distal colon, our results suggest that tumors in the distal portion of the large intestine may be particularly associated with meat consumption. It is possible that concentration of stool in the distal portion of the large intestine may contribute to higher cancer risk by increasing exposure to carcinogens as a result of water resorption during transit through the large intestine.

Our study had several limitations in addition to the measurement error inherent in studies based on FFQs.77 The 1982 questionnaire did not assess the number of servings of meat per day and could not differentiate persons who ate multiple servings from those who ate meat only once per day; we were also unable to estimate total energy intake from the 1982 diet questionnaire. We had no information on meat cooking methods to estimate exposure to heterocyclic amines or other specific carcinogens produced from pyrolysis of meat7882; our reliance on self-reported data on preference for doneness of meat was likely a crude proxy of the relevant exposures. Although heterocyclic amines are potent mutagens in the Ames assay and are carcinogenic in animal studies, the impact of these compounds on colorectal carcinogenesis in humans is less clear,8183 primarily due to the difficulties in measuring exposure and possible interactions between meat and other dietary constituents or genetic susceptibility.9,84 We had no information on family history of colorectal cancer from the 1992/1993 questionnaire to update this important variable, which could potentially modify the association between meat intake and risk of colorectal cancer. No information was collected on examination by sigmoidoscopy, colonoscopy, or fecal occult blood test in either the 1982 or 1992/1993 questionnaires. However, in 1997, persons who reported long-term high consumption of red meat were less likely (23%) to have had endoscopy for screening than those persons who reported long-term low intake of red meat (34%). It is difficult to predict the net effect of endoscopy on colorectal cancer incidence. On the one hand, endoscopic removal of precancerous lesions could contribute to lower risk; however, endoscopy could accelerate the diagnosis of some tumors that might not otherwise have been identified during the follow-up period.

The main strengths of this study are its size, the availability of dietary and other exposure information collected prospectively from respondents at 2 time points, and information on major potential confounders. The sample size allowed us to obtain stable estimates of risk and to show differences by colorectal subsite. Our results demonstrate the potential value of examining long-term meat consumption in assessing risk and strengthen the evidence that prolonged high consumption of red and processed meat may increase the risk of cancer in the distal portion of the large intestine.

Corresponding Author: Michael J. Thun, MD, MS, Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Rd, NE, Atlanta, GA 30329-4251 (mthun@cancer.org).

Author Contributions: As principal investigator, Dr Chao had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Chao, Thun, McCullough.

Acquisition of data: Thun, Rodriguez, Calle.

Analysis and interpretation of data: Chao, Thun, Connell, McCullough, Jacobs, Flanders, Rodriguez, Sinha, Calle.

Drafting of the manuscript: Chao, Thun.

Critical revision of the manuscript for important intellectual content: Chao, Thun, Connell, McCullough, Jacobs, Flanders, Rodriguez, Sinha, Calle.

Statistical analysis: Chao, Connell, Flanders.

Obtained funding: Thun, Calle.

Administrative, technical, or material support: Chao, Thun, McCullough.

Study supervision: Thun, Calle.

Funding/Support: The American Cancer Society (ACS) funds the creation, maintenance, and updating of the Cancer Prevention Study II Nutrition Cohort. All of the authors were employed by either the ACS or the National Cancer Institute (NCI) during the course of the study. Dr Chao was supported by the ACS and Public Health Service grant K07CA75062 from the NCI, National Institutes of Health, Department of Health and Human Services, until her relocation to Zambia in July 2004.

Role of the Sponsor: Staff in the Epidemiology and Surveillance Research Department of ACS designed and conducted the study, including collection, analysis, interpretation, and presentation of the manuscript. No staff at ACS or NCI, other than study investigators, reviewed or approved the manuscript.

Acknowledgment: We express sincere gratitude to all CPS II Nutrition Cohort participants and to each member of the CPS II Study Management Group.

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Shannon J, White E, Shattuck AL.  et al.  Relationship of food groups and water intake to colon cancer risk.  Cancer Epidemiol Biomarkers Prev. 1996;5:495-502
PubMed
Le Marchand L, Wilkens LR, Hankin JH, Kolonel LN, Lyu LC. A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii (United States): lipids and foods of animal origin.  Cancer Causes Control. 1997;8:637-648
PubMed   |  Link to Article
Kampman E, Slattery ML, Bigler J.  et al.  Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study.  Cancer Epidemiol Biomarkers Prev. 1999;8:15-24
PubMed
Pickle LW, Greene MH, Ziegler RG.  et al.  Colorectal cancer in rural Nebraska.  Cancer Res. 1984;44:363-369
PubMed
Wohlleb JC, Hunter CF, Blass B.  et al.  Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations.  Int J Cancer. 1990;46:22-30
PubMed   |  Link to Article
Butler LM, Sinha R, Millikan RC.  et al.  Heterocyclic amines, meat intake, and association with colon cancer in a population-based study.  Am J Epidemiol. 2003;157:434-445
PubMed   |  Link to Article
Kune S, Kune GA, Watson LF. Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study.  Nutr Cancer. 1987;9:21-42
PubMed   |  Link to Article
Kampman E, Verhoeven D, Sloots L.  et al.  Vegetable and animal products as determinants of colon cancer risk in Dutch men and women.  Cancer Causes Control. 1995;6:225-234
PubMed   |  Link to Article
Macquart-Moulin G, Riboli E, Cornee J.  et al.  Case-control study on colorectal cancer and diet in Marseilles.  Int J Cancer. 1986;38:183-191
PubMed   |  Link to Article
Vlajinac H, Adanja B, Jarebinski M. Case-control study of the relationship of diet and colon cancer.  Arch Geschwulstforsch. 1987;57:493-498
PubMed
La Vecchia C, Negri E, Decarli A.  et al.  A case-control study of diet and colorectal cancer in northern Italy.  Int J Cancer. 1988;41:492-498
PubMed   |  Link to Article
Tuyns AJ, Kaaks R, Haelterman M. Colorectal cancer and the consumption of foods: a case-control study in Belgium.  Nutr Cancer. 1988;11:189-204
PubMed   |  Link to Article
Benito E, Obrador A, Stiggelbout A.  et al.  A population-based case-control study of colorectal cancer in Majorca, I: dietary factors.  Int J Cancer. 1990;45:69-76
PubMed   |  Link to Article
Gerhardsson de Verdier M, Hagman U, Peters RK.  et al.  Meat cooking methods and colorectal cancer: a case-referent study in Stockholm.  Int J Cancer. 1991;49:520-525
PubMed   |  Link to Article
Bidoli E, Franceschi S, Talamini R.  et al.  Food consumption and cancer of the colon and rectum in northeastern Italy.  Int J Cancer. 1992;50:223-229
PubMed   |  Link to Article
La Vecchia C, Ferraroni M, Mezzetti M.  et al.  Attributable risks for colorectal cancer in northern Italy.  Int J Cancer. 1996;66:60-64
PubMed   |  Link to Article
Augustsson K, Skog K, Jägerstad M, Dickman PW, Steineck G. Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: population-based study.  Lancet. 1999;353:703-707
PubMed   |  Link to Article
Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S. Food groups and colorectal cancer risk.  Br J Cancer. 1999;79:1283-1287
PubMed   |  Link to Article
Boutron-Ruault MC, Senesse P, Faivre J, Chatelain N, Belghiti C, Méance S. Foods as risk factors for colorectal cancer: a case-control study in Burgundy (France).  Eur J Cancer Prev. 1999;8:229-235
PubMed   |  Link to Article
Haenszel W, Berg JW, Segi M.  et al.  Large-bowel cancer in Hawaiian Japanese.  J Natl Cancer Inst. 1973;51:1765-1779
PubMed
Haenszel W, Locke FB, Segi M. A case-control study of large bowel cancer in Japan.  J Natl Cancer Inst. 1980;64:17-22
PubMed
Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan.  Jpn J Cancer Res. 1985;76:705-716
PubMed
Lee HP, Gourley L, Duffy SW.  et al.  Colorectal cancer and diet in an Asian population: a case-control study among Singapore Chinese.  Int J Cancer. 1989;43:1007-1016
PubMed   |  Link to Article
Hu JF, Liu YY, Yu YK.  et al.  Diet and cancer of the colon and rectum: a case-control study in China.  Int J Epidemiol. 1991;20:362-367
PubMed   |  Link to Article
Murata M, Tagawa M, Watanabe S.  et al.  Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.  Jpn J Cancer Res. 1999;90:711-719
PubMed   |  Link to Article
Seow A, Quah SR, Nyam D, Straughan PT, Chua T, Aw TC. Good groups and the risk of colorectal carcinoma in an Asian population.  Cancer. 2002;95:2390-2396
PubMed   |  Link to Article
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Intake of fat, meat, and fiber in relation to risk of colon cancer in men.  Cancer Res. 1994;54:2390-2397
PubMed
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.  N Engl J Med. 1990;323:1664-1672
PubMed   |  Link to Article
Chen J, Stampfer MJ, Hough HL.  et al.  A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer.  Cancer Res. 1998;58:3307-3311
PubMed
Singh PN, Fraser GE. Dietary risk factors for colon cancer in a low risk population.  Am J Epidemiol. 1998;148:761-774
PubMed   |  Link to Article
Hsing AW, McLaughlin JK, Chow WH.  et al.  Risk factors for colorectal cancer in a prospective study among US white men.  Int J Cancer. 1998;77:549-553
PubMed   |  Link to Article
Phillips RL, Snowdon DA. Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists.  J Natl Cancer Inst. 1985;74:307-317
PubMed
Bostick RM, Potter JD, Kushi LH.  et al.  Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States).  Cancer Causes Control. 1994;5:38-52
PubMed   |  Link to Article
Kato I, Akhmedkhanov A, Koenig K, Toniolo PG, Shore RE, Riboli E. Prospective study of diet and female colorectal cancer: the New York University Women’s Health Study.  Nutr Cancer. 1997;28:276-281
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Thun MJ, Calle EE, Namboodiri MM.  et al.  Risk factors for fatal colon cancer in a large prospective study.  J Natl Cancer Inst. 1992;84:1491-1500
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Flood A, Velie EM, Sinha R.  et al.  Meat, fat, and their subtypes as risk factors for colorectal cancer in a prospective cohort of women.  Am J Epidemiol. 2003;158:59-68
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Goldbohm RA, van den Brandt PA, van’t Veer P.  et al.  A prospective cohort study on the relation between meat consumption and the risk of colon cancer.  Cancer Res. 1994;54:718-723
PubMed
Knekt P, Steineck G, Järvinen R, Hakulinen T, Aromaa A. Intake of fried meat and risk of cancer: a follow-up study in Finland.  Int J Cancer. 1994;59:756-760
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Järvinen R, Knekt P, Hakulinen T, Rissanen H, Heliövaara M. Dietary fat, cholesterol and colorectal cancer in a prospective study.  Br J Cancer. 2001;85:357-361
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Gaard M, Tretli S, Loken EB. Dietary factors and risk of colon cancer: a prospective study of 50,535 young Norwegian men and women.  Eur J Cancer Prev. 1996;5:445-454
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Pietinen P, Malila N, Virtanen M.  et al.  Diet and risk of colorectal cancer in a cohort of Finnish men.  Cancer Causes Control. 1999;10:387-396
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Tiemersma EW, Kampman E, Bueno de Mesquita HB.  et al.  Meat consumption, cigarette smoking, and genetic susceptibility in the etiology of colorectal cancer: results from a Dutch prospective study.  Cancer Causes Control. 2002;13:383-393
PubMed   |  Link to Article
Norat T, Lukanova A, Ferrari P, Riboli E. Meat consumption and colorectal cancer risk: dose-response meta-analysis of epidemiological studies.  Int J Cancer. 2002;98:241-256
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Sandhu MS, White IR, McPherson K. Systematic review of the prospective cohort studies on meat consumption and colorectal cancer risk: a meta-analytical approach.  Cancer Epidemiol Biomarkers Prev. 2001;10:439-446
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Cross AJ, Pollock JRA, Bingham SA. Haem, not protein or inorganic iron, is responsible for endogenous intestinal N-nitrosation arising from red meat.  Cancer Res. 2003;63:2358-2360
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Hughes R, Pollock JRA, Bingham S. Effect of vegetables, tea, and soy on endogenous N-nitrosation, fecal ammonia, and fecal water genotoxicity during a high red meat diet in humans.  Nutr Cancer. 2002;42:70-77
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Al-Taie OH, Seufert J, Karvar S.  et al.  Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenomas.  Nutr Cancer. 2003;46:125-130
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Fernandez-Banares F, Cabre E, Esteve M.  et al.  Serum selenium and risk of large size colorectal adenomas in a geographical area with a low selenium status.  Am J Gastroenterol. 2002;97:2103-2108
PubMed
Yang CX, Takezaki T, Hirose K, Inoue M, Huang XE, Tajima K. Fish consumption and colorectal cancer: a case-reference study in Japan.  Eur J Cancer Prev. 2003;12:109-115
PubMed   |  Link to Article
Kato T, Hancock RL, Mohammadpour H.  et al.  Influence of ometa-3 fatty acids on the growth of human colon carcinoma in nude mice.  Cancer Lett. 2002;187:169-177
PubMed   |  Link to Article
Narayanan BA, Narayanan NK, Simi B, Reddy BS. Modulation of inducible nitric oxide synthase and related proinflammatory genes by the omega-3 fatty acid docosahexaenoic acid in human colon cancer cells.  Cancer Res. 2003;63:972-979
PubMed
English DR, Macinnins RJ, Hodge AM, Hopper JL, Haydon AM, Giles GG. Red meat, chicken, and fish consumption and risk of colorectal cancer.  Cancer Epidemiol Biomarkers Prev. 2004;13:1509-1514
PubMed
Murtaugh MA, Ma K, Sweeney C.  et al.  Meat consumption patterns and preparation, genetic variants of metabolic enzymes, and their association with rectal cancer in men and women.  J Nutr. 2004;134:776-784
PubMed
Kipnis V, Subar AF, Midthune D.  et al.  Structure of dietary measurement error: results of the OPEN Biomarker Study.  Am J Epidemiol. 2003;158:14-21
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Layton DW, Bogen KT, Knize MG, Hatch FT, Johnson VM, Felton JS. Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research.  Carcinogenesis. 1995;16:39-52
PubMed   |  Link to Article
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PubMed
Sinha R, Rothman N. Exposure assessment of heterocyclic amines (HCAs) in epidemiologic studies.  Mutat Res. 1997;376:195-202
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Sinha R, Rothman N, Brown ED.  et al.  High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method.  Cancer Res. 1995;55:4516-4519
PubMed
Weisburger JH. Comments on the history and importance of aromatic and heterocyclic amines in public health.  Mutat Res. 2002;506-507:9-20
PubMed   |  Link to Article
Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN. Diet, acetylator phenotype, and risk of colorectal neoplasia.  Lancet. 1996;347:1372-1374
PubMed   |  Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1. Selected Characteristics of Study Participants by Red Meat Consumption in the Year Before Study Enrollment*
Table Graphic Jump LocationTable 2. Meat Consumption Reported by Men and Women in 1992/1993 and Colon Cancer Cases by Quintile for All 3 Models*
Table Graphic Jump LocationTable 3. Meat Consumption of Men and Women Combined Reported in 1992/1993 and Proximal Colon, Distal Colon, and Rectal Cancer Cases by Quintile*
Table Graphic Jump LocationTable 4. Meat Consumption and Meat Intake of Men and Women Reported in 1982 and 1992/1993, and Cases of Proximal Colon, Distal Colon, and Rectal Cancer*

References

Giovannucci E, Stampfer MJ, Colditz G, Rimm EB, Willett WC. Relationship of diet to risk of colorectal adenoma in men.  J Natl Cancer Inst. 1992;84:91-98
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PubMed   |  Link to Article
Peters RK, Pike MC, Garabrant D, Mack TM. Diet and colon cancer in Los Angeles County, California.  Cancer Causes Control. 1992;3:457-473
PubMed   |  Link to Article
Shannon J, White E, Shattuck AL.  et al.  Relationship of food groups and water intake to colon cancer risk.  Cancer Epidemiol Biomarkers Prev. 1996;5:495-502
PubMed
Le Marchand L, Wilkens LR, Hankin JH, Kolonel LN, Lyu LC. A case-control study of diet and colorectal cancer in a multiethnic population in Hawaii (United States): lipids and foods of animal origin.  Cancer Causes Control. 1997;8:637-648
PubMed   |  Link to Article
Kampman E, Slattery ML, Bigler J.  et al.  Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study.  Cancer Epidemiol Biomarkers Prev. 1999;8:15-24
PubMed
Pickle LW, Greene MH, Ziegler RG.  et al.  Colorectal cancer in rural Nebraska.  Cancer Res. 1984;44:363-369
PubMed
Wohlleb JC, Hunter CF, Blass B.  et al.  Aromatic amine acetyltransferase as a marker for colorectal cancer: environmental and demographic associations.  Int J Cancer. 1990;46:22-30
PubMed   |  Link to Article
Butler LM, Sinha R, Millikan RC.  et al.  Heterocyclic amines, meat intake, and association with colon cancer in a population-based study.  Am J Epidemiol. 2003;157:434-445
PubMed   |  Link to Article
Kune S, Kune GA, Watson LF. Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study.  Nutr Cancer. 1987;9:21-42
PubMed   |  Link to Article
Kampman E, Verhoeven D, Sloots L.  et al.  Vegetable and animal products as determinants of colon cancer risk in Dutch men and women.  Cancer Causes Control. 1995;6:225-234
PubMed   |  Link to Article
Macquart-Moulin G, Riboli E, Cornee J.  et al.  Case-control study on colorectal cancer and diet in Marseilles.  Int J Cancer. 1986;38:183-191
PubMed   |  Link to Article
Vlajinac H, Adanja B, Jarebinski M. Case-control study of the relationship of diet and colon cancer.  Arch Geschwulstforsch. 1987;57:493-498
PubMed
La Vecchia C, Negri E, Decarli A.  et al.  A case-control study of diet and colorectal cancer in northern Italy.  Int J Cancer. 1988;41:492-498
PubMed   |  Link to Article
Tuyns AJ, Kaaks R, Haelterman M. Colorectal cancer and the consumption of foods: a case-control study in Belgium.  Nutr Cancer. 1988;11:189-204
PubMed   |  Link to Article
Benito E, Obrador A, Stiggelbout A.  et al.  A population-based case-control study of colorectal cancer in Majorca, I: dietary factors.  Int J Cancer. 1990;45:69-76
PubMed   |  Link to Article
Gerhardsson de Verdier M, Hagman U, Peters RK.  et al.  Meat cooking methods and colorectal cancer: a case-referent study in Stockholm.  Int J Cancer. 1991;49:520-525
PubMed   |  Link to Article
Bidoli E, Franceschi S, Talamini R.  et al.  Food consumption and cancer of the colon and rectum in northeastern Italy.  Int J Cancer. 1992;50:223-229
PubMed   |  Link to Article
La Vecchia C, Ferraroni M, Mezzetti M.  et al.  Attributable risks for colorectal cancer in northern Italy.  Int J Cancer. 1996;66:60-64
PubMed   |  Link to Article
Augustsson K, Skog K, Jägerstad M, Dickman PW, Steineck G. Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: population-based study.  Lancet. 1999;353:703-707
PubMed   |  Link to Article
Levi F, Pasche C, La Vecchia C, Lucchini F, Franceschi S. Food groups and colorectal cancer risk.  Br J Cancer. 1999;79:1283-1287
PubMed   |  Link to Article
Boutron-Ruault MC, Senesse P, Faivre J, Chatelain N, Belghiti C, Méance S. Foods as risk factors for colorectal cancer: a case-control study in Burgundy (France).  Eur J Cancer Prev. 1999;8:229-235
PubMed   |  Link to Article
Haenszel W, Berg JW, Segi M.  et al.  Large-bowel cancer in Hawaiian Japanese.  J Natl Cancer Inst. 1973;51:1765-1779
PubMed
Haenszel W, Locke FB, Segi M. A case-control study of large bowel cancer in Japan.  J Natl Cancer Inst. 1980;64:17-22
PubMed
Tajima K, Tominaga S. Dietary habits and gastro-intestinal cancers: a comparative case-control study of stomach and large intestinal cancers in Nagoya, Japan.  Jpn J Cancer Res. 1985;76:705-716
PubMed
Lee HP, Gourley L, Duffy SW.  et al.  Colorectal cancer and diet in an Asian population: a case-control study among Singapore Chinese.  Int J Cancer. 1989;43:1007-1016
PubMed   |  Link to Article
Hu JF, Liu YY, Yu YK.  et al.  Diet and cancer of the colon and rectum: a case-control study in China.  Int J Epidemiol. 1991;20:362-367
PubMed   |  Link to Article
Murata M, Tagawa M, Watanabe S.  et al.  Genotype difference of aldehyde dehydrogenase 2 gene in alcohol drinkers influences the incidence of Japanese colorectal cancer patients.  Jpn J Cancer Res. 1999;90:711-719
PubMed   |  Link to Article
Seow A, Quah SR, Nyam D, Straughan PT, Chua T, Aw TC. Good groups and the risk of colorectal carcinoma in an Asian population.  Cancer. 2002;95:2390-2396
PubMed   |  Link to Article
Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC. Intake of fat, meat, and fiber in relation to risk of colon cancer in men.  Cancer Res. 1994;54:2390-2397
PubMed
Willett WC, Stampfer MJ, Colditz GA, Rosner BA, Speizer FE. Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women.  N Engl J Med. 1990;323:1664-1672
PubMed   |  Link to Article
Chen J, Stampfer MJ, Hough HL.  et al.  A prospective study of N-acetyltransferase genotype, red meat intake, and risk of colorectal cancer.  Cancer Res. 1998;58:3307-3311
PubMed
Singh PN, Fraser GE. Dietary risk factors for colon cancer in a low risk population.  Am J Epidemiol. 1998;148:761-774
PubMed   |  Link to Article
Hsing AW, McLaughlin JK, Chow WH.  et al.  Risk factors for colorectal cancer in a prospective study among US white men.  Int J Cancer. 1998;77:549-553
PubMed   |  Link to Article
Phillips RL, Snowdon DA. Dietary relationships with fatal colorectal cancer among Seventh-Day Adventists.  J Natl Cancer Inst. 1985;74:307-317
PubMed
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