Incident Colon and Rectal Cancer. Part 2
The 1992/1993 FFQ was validated among 441 Nutrition Cohort members who completed four 24-hour dietary recall interviews and a repeat FFQ. 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. 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. 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).
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.”
Meat Consumption and Risk of Colorectal Cancer. Part 2
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%. Mortality follow-up of the entire CPS II Nutrition Cohort 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. 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.
Meat Consumption and Risk of Colorectal Cancer. Part 2
Five of 1033-42 US prospective studies of colorectal cancer reported positive associations with red or processed meat intake, although some associations did not reach statistical significance. European prospective studies have generally reported no association with fresh or total meat but positive associations with cured or processed meat, sausages, or smoked/salted fish. High consumption of poultry or fish has been inconsistently associated with higher or lower risk of colorectal cancer; some studies have found no association. Only 2 prospective studies 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-analysis 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.
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. 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.
Meat Consumption and Risk of Colorectal Cancer
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 1.3.1-3 Case-control studies 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, and men and women combined, but not in analyses that included only women. Case-control studies of colorectal cancer among Asians in the United States or Asia have more consistently reported a positive association with red, processed, or total meats.