Glycemic index, glycemic load, and carbohydrate intake in relation to risk of distal colorectal adenoma in women.

Case-control studies and a cohort study have shown inconsistent associations between a high glycemic index or a high glycemic load and risk of colorectal cancer. These dietary variables have not been examined in relation to risk of colorectal adenoma. We thus examined the associations between dietary glycemic index, glycemic load, and carbohydrate intake with risk of adenoma of the distal colon or rectum among 34,428 US women who were initially free of cancer or polyps, who completed a semi-quantitative food-frequency questionnaire in 1980, and who underwent endoscopy from 1980 through 1998. 1,715 adenoma cases (704 large adenomas, 894 small adenomas, 1,277 distal colon adenomas, and 504 rectal adenomas) were documented during 18 years of follow-up. Dietary glycemic index, glycemic load, and carbohydrate intake were not related to risk of total colorectal adenoma after adjustment for age and established risk factors [relative risk (RR) for extreme quintiles of glycemic index = 1.11, 95% confidence interval (CI) 0.94-1.32, P for trend = 0.66; RR for glycemic load = 0.92, 95% CI 0.76-1.11, P for trend = 0.63; RR for carbohydrate intake = 0.90, 95% CI 0.73-1.11, P for trend = 0.64]. In addition, no significant associations were found for large or small adenoma, distal colon or rectal adenoma, or across strata of body mass index. Our findings do not support the hypothesis that a high glycemic index diet, a high glycemic load diet, or high carbohydrate intake overall are associated with risk of colorectal adenoma.     

Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women.

Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CI), 0.84-1.27, P(trend) = 0.66; RR for extreme quintiles of n-3/n-6 ratio = 1.02; 95% CI, 0.83-1.25; P(trend) = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P(trend) = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P(trend) = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas.     

A comparative case-control study of colorectal cancer and adenoma

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer.     

Fruit and vegetable consumption and colorectal adenomas in the Nurses' Health Study

Consumption of fruits and vegetables may confer protection from colorectal adenomas, but the limited observational and interventional evidence is inconclusive. We examined the association between fruit and vegetable consumption and the prevalence and incidence of adenomas of the distal colon and rectum in the Nurses' Health Study (NHS). We used data from 34,467 women in the NHS who had undergone colonoscopy or sigmoidoscopy during follow-up between 1980 and 1998. Consumption of fruits and vegetables was assessed in 1980, 1984, 1986, 1990, and 1994 using a semiquantitative food frequency questionnaire; 1,720 prevalent cases of adenoma of the distal colon and rectum were diagnosed between 1980 and 1998. Frequent consumption of fruit was inversely related to the risk of being diagnosed with polyps, whereas little association was found for vegetable consumption. Women who reported consuming five or more servings of fruit a day had an odds ratio (OR) of 0.60 [95% confidence interval (95% CI), 0.44-0.81] for developing colorectal adenomas compared with women who consumed only one or fewer servings of fruit per day, after adjustment for relevant covariates (P(trend) = 0.001). The respective OR for vegetable consumption was 0.82 (95% CI, 0.65-1.05; P(trend) = 0.1). Women who consumed four or more servings of legumes per week had a lower incidence of colorectal adenomas than women who reported consuming one serving per week or less (OR, 0.67; 95% CI, 0.51-0.90; P(trend) = 0.005). Frequent consumption of fruit may reduce the risk of colorectal adenomas.     

A Comparative Case-Control Study of Colorectal Cancer and Adenoma

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risk (RR)=0.59, 95% confidence interval (CI): 0.39–0.89) and rectal cancer (RR=0.46, 95% CI: 0.25–0.84). Daily beans intake was associated with lower risk of colon adenoma (RR=0.58, 95% CI: 0.37–0.91 for the proximal colon and RR=0.63, 95% CI: 0.45–0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR=0.42, 95% CI: 0.22–0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR=0.67, 95% CI: 0.45–0.99 for the proximal colon and RR=0.70, 95% CI: 0.52–0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR=1.95, 95% CI: 1.15–3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risks of both colorectal adenoma and cancer.     

Reproductive risk factors for colorectal adenomatous polyps (New York City,NY, United States)

Events of reproductive life, such as parity and age at menarche, have been found in some but not all studies to be associated with risk for colorectal cancer in females. Because adenomatous polyps (adenomas) are precursors of colorectal cancer, we investigated whether reproductive variables were associated with colorectal adenomas. We conducted a case-control study among patients examined in three colonoscopy practices in New York City (NY, United States) from 1986 to 1988. Adenoma cases (n=128) were defined as women who had an adenoma detected at the index colonoscopy with no history of inflammatory bowel disease, adenomas, or cancer. Controls (n=283) were women with a normal index colonoscopy and no history of inflammatory bowel disease, adenomas, or cancer. The adjusted odds ratio (OR) for the association of early menarche (age less than 13 years) with adenomas was 0.6 (95 percent confidence interval=0.4–0.9). Parity, history of spontaneous or induced abortion, infertility, type of menopause, age at menopause, use of oral contraceptives, and use of menopausal hormone replacement therapy were not associated statistically significantly with adenoma risk, although some possible trends were observed. Our findings do not implicate reproductive events, nulliparity, or overexposure to estrogens or to menstrual cycles as mechanisms of increased risk for colorectal neoplasia.This work was supported by grants from the US National Cancer Institute (RO1-CA37196 and T32-CA09529).     

Diet,alcohol, and smoking and the occurrence of hyperplastic polyps of the colon and rectum (United States)

Hyperplastic polyps of the colon reveal a geographic distribution similar to that of colorectal cancer and adenomatous polyps. However, unlike adenomas—known precursors of colorectal cancer—little is known about the etiology or clinical significance of the hyperplastic polyp. In this prospective study, we set out to determine the main dietary and other lifestyle factors in the United States that might be associated with this lesion. Hyperplastic polyps of the distal colon and rectum were diagnosed in 219 of 12,922 men of the Health Professionals Follow-up Study having had an endoscopic procedure between 1986 and 1992, and 175 of 15,339 women of the Nurses' Health Study who had undergone an endoscopy for a variety of reasons between 1980 and 1990. After adjusting for age, family history of colon cancer, history of previous endoscopy, and total energy intake using multiple logistic regression, those consuming 30 g or more of alcohol per day were at increased risk relative to nondrinkers among men (relative risk [RR]=1.69; 95 percent confidence interval [CI]=1.01–2.80) and women (RR=1.79, CI=1.02–3.15). Current smoking also was found to be associated strongly positively with hyperplastic polyps in men (RR=2.45, CI=1.59–3.75) and women (RR=1.96, CI=1.16–2.86). High intake of folate was associated inversely with risk in both men (RR=0.74, CI=0.49–1.11, between high and low intakes of folate) and women (RR=0.45, CI=0.28–0.74, between high and low intakes of folate). Among macronutrients, a suggestive increase in risk existed with intake of animal fat, although this was attenuated in the full multivariate model (RR[men]=1.48, CI=0.94–2.41, and RR [women]=1.22, CI=0.77–1.94) between high and low quantities of animal fat intake. These prospective data provide evidence of associations between low folate intake, alcohol consumption, and current cigarette smoking, and risk of hyperplastic polyps of the distal colon and rectum. These same factors also have been found to be related to adenoma and cancer of the colon. The hyperplastic polyp is an indicator of populations at high risk for colorectal carcinoma, and it also may serve as a marker for factors that influence neoplastic evolution.Drs Giovannucci, Stampfer, Colditz, and Willett are with the Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA. Authors also are affiliated with: the Department of Nutrition, Harvard School of Public Health, Boston, MA (Drs Kearney, Rimm, Stampfer, Ascherio, and Willett); the Department of Epidemiology, Harvard School of Public Health (Drs Rimm, Stampfer, Colditz, Ascherio, and Willett); and the Department of Surgery, New England Deaconess Hospital, Boston, MA (Dr Bleday). Address correspondence to Dr Giovannucci, Channing Laboratory, 180 Longwood Avenue, Boston, MA 02115, USA. This project was supported by research grants number CA 55075 and HL 35464 from the National Institutes of Health and Special Institution Grant No. 18 from the American Cancer Society. Dr Colditz. was supported by a Faculty Research Award (FRA-398) from the American Cancer Society.     

Tobacco smoking and colorectal hyperplastic and adenomatous polyps.

Colorectal adenomas and possibly some hyperplastic polyps are precursors of colorectal cancer. Tobacco use is associated in epidemiologic studies with these polyps, although links between smoking and colorectal cancer are less consistent. To characterize the role of tobacco in early colorectal carcinogenesis, we compared tobacco use among 4,383 subjects with histologically verified benign (hyperplastic or adenomatous) polyps of the distal colon (descending colon, sigmoid, and rectum) with tobacco use among 33,667 subjects who were endoscopy negative for distal colon tumors, in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Trial, a randomized trial of flexible sigmoidoscopy. Risks, estimated by the odds ratio (OR), associated with current cigarette use were OR = 4.4 [95% confidence interval (95% CI), 3.7-5.2] for hyperplastic polyps only, OR = 1.8 (95% CI, 1.5-2.1) for adenomas only, and OR = 6.2 (95% CI, 4.7-8.3) for subjects with both hyperplastic and adenomatous polyps concurrently. Effects were weaker among ex smokers; the smoking-associated ORs remained consistently higher for hyperplastic polyps. This pattern was also seen in relation to cigarettes smoked per day, smoking duration, and pack-years. Tobacco-associated risks for multiple polyps were also stronger when hyperplastic disease was involved. In conclusion, tobacco use, particularly recent use, increases risk for both adenomatous and hyperplastic polyps, but the risks are substantially greater for hyperplastic lesions.     

A case-control study of male colorectal cancer in Aichi Prefecture, Japan: with special reference to occupational activity level, drinking habits and family history

The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979-1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38-2.67) for proximal colon cancer, 1.52 (95% CI: 1.19-1.94) for distal colon cancer and 1.38 (95% CI: 1.17-1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13-1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62-2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19-5.29) for proximal colon cancer, 2.54 (95% CI: 1.73-3.75) for distal colon cancer and 1.78 (95% CI: 1.28-2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40-45.78) for proximal colon cancer, 10.55 (95% CI: 4.24-26.27) for distal colon cancer and 6.69 (95% CI: 3.12-14.36) for rectal cancer.     

Relationship of diet to risk of colorectal adenoma in men.

BACKGROUND: Rates of colorectal cancer in various countries are strongly correlated with per-capita consumption of red meat and animal fat and inversely associated with fiber consumption. There have been few studies, however, of dietary risk factors for colorectal adenomas, which are precursors of cancer. PURPOSE: Our purpose was to determine prospectively the relationship between dietary factors and risk of colorectal adenomas. METHODS: Using data from the Health Professionals Follow-up Study, we documented 170 cases of adenomas of the left colon or rectum in 7284 male health professionals who completed a food-frequency questionnaire in 1986 and who had a colonoscopy or sigmoidoscopy between 1986 and 1988. Relative risk (RR) of adenoma was determined according to quintiles of nutrient intakes. RESULTS: After adjustment for total energy intake, saturated fat was positively associated with risk of colorectal adenoma (P for trend = .006); RR for the highest versus the lowest quintile of intake was 2.0 (95% confidence interval [CI] = 1.2-3.2). Dietary fiber was inversely associated with risk of adenoma (P for trend less than .0001); RR for men in the highest versus the lowest quintile was 0.36 (95% CI = 0.22-0.60). All sources of fiber (vegetables, fruits, and grains) were associated with decreased risk of adenoma. For subjects on a high-saturated fat, low-fiber diet, the RR was 3.7 (95% CI = 1.5-8.8) compared with those on a low-saturated fat, high-fiber diet. The ratio of the intake of red meat to the intake of chicken and fish was positively associated with risk of adenoma (P for trend = .02). CONCLUSIONS: These prospective data provide evidence for the hypothesis that a diet high in saturated fat and low in fiber increases the risk of colorectal adenoma. They also support existing recommendations to substitute chicken and fish for red meat in the diet and to increase intake of vegetables, fruits, and grains to reduce risk of colorectal cancer.     

Predictors of metachronous colorectal neoplasms in sporadic adenoma patients

Our objective was to assess the overall risk of subsequent colorectal neoplasms (cancer or adenoma) in relation with the various characteristics of the index lesion in a cohort of patients who underwent endoscopic polypectomies of colorectal adenomas. A total of 1086 patients with adenomas of the large bowel were reported between 1979 and 1999 at the National Cancer Institute of Milan during a screening program for colorectal carcinoma. Data on patients who had colonoscopic examinations and treatments were collected prospectively. The relation between colorectal cancer (CRC) and adenoma features was assessed by computing the hazard ratio (HR) values and corresponding confidence intervals (95% CI) according to Cox proportional hazard models. Of the 1086 eligible patients (487 females, 579 males), 736 had single adenomas (67.7%) and 350 had multiple adenomas (32.3%). Histologic examination revealed 772 cases of tubular adenoma (73%), 205 cases of tubulovillous adenoma and 80 cases of villous adenoma (7.5%). Severe dysplasia was found in 3.3% of the cases. During the 11393 person-years of follow-up, with an average time of surveillance of 10.5 years, colorectal carcinomas developed in 10 patients (0.8%) and a new adenoma in 323 patients (29%). Multivariate analysis showed that male gender (HR 1.6; 95% CI 1.3-2.0), multiple polyps (HR 1.6; 95% CI 1.3-2.0), polyps larger than 2 cm (HR 1.5; 95% CI 1.1-2.1), tubulovillous and villous histology (HR 1.3; 95% CI 1.0-1.6 and HR 1.8; 95% CI 1.2-2.6, respectively) at index polypectomy were statistically significant risk factors for developing metachronous adenomatous polyps. The standardized incidence rates (SIR) for CRC was 0.52 (95% CI 0.25-0.95). The SIR was increased in subjects with severe dysplasia (2.8; 95% CI 0.34-1.02). Some features of large bowel adenomas are strongly correlated with an increased risk of metachronous adenomas and colorectal cancer. However, the endoscopic polypectomy is able to reduce by 50% the incidence of CRC in patients with large bowel adenomas.     

K-ras mutations in incident sporadic colorectal adenomas

BACKGROUND: Although K-ras is the most frequently mutated protooncogene in colorectal carcinoma, the specific role and timing of K-ras mutations in colorectal carcinogenesis remains controversial. In the current study, the authors investigated associations with K-ras mutation in incident sporadic colorectal adenomas that occurred during a chemoprevention trial of calcium supplementation. METHODS: K-ras genotyping was performed on 303 colorectal adenomas that were removed from 207 participants during the follow-up phase of the Calcium Polyp Prevention Study. Mutations in codons 12 or 13 of K-ras were detected by denaturing high-performance liquid chromatography and were confirmed by direct sequencing. RESULTS: The adenomas analyzed had a mean estimated size of 0.5 cm, and 3.0% were identified with mutations (95% confidence interval [95% CI], 1.3-4.4%). These mutations were more common in larger adenomas (risk ratio [RR], 12.7 for tumors that measured > 0.5 cm vs. < or = 0.5 cm; 95% CI, 2.7-59.7), in adenomas with more advanced histology (RR, 20.6 for tubulovillous/villous vs. tubular; 95% CI, 4.4-96.0), and in adenomas that were located in the rectum compared with the colon (RR, 8.4; 95% CI, 2.3-30.5). CONCLUSIONS: Compared with previous studies, the current analysis was novel, because it focused on incident adenomas that were diagnosed within a few years of a previous "clean" colonoscopy. The results provided evidence for a very low rate of K-ras mutation among these small, early adenomas and strong support for a role of K-ras mutations in adenoma progression.     

Screening endoscopy and risk of colorectal cancer in United States men

Objectives: The purpose of this study was to describe the effect of screening endoscopy (sigmoidoscopy or colonoscopy) on colorectal cancer incidence and mortality. Methods: We used data from a prospective cohort study of 24,744 men aged 40 to 75 years in 1986, free from cancer and colon polyps, followed until 1994. The outcomes are diagnosis of colorectal cancer and death from colorectal cancer. Results: Screening endoscopy in 1986-87 was associated with a lower risk of all colorectal cancer (multivariate relative risk [RR]=0.58, 95 percent confidence interval [CI]=0.36-0.96); cancer in the distal colon or rectum (multivariate RR=0.40, CI=0.19-0.84); Dukes stage A&B (multivariate RR=0.66, CI=0.35-1.25); and Dukes stage C&D (multivariate RR=0.50, CI=0.20-1.26) colorectal cancer; and death from colorectal cancer (multivariate RR=0.56, CI=0.20-1.60), after adjusting for age and a wide range of colon cancer risk factors. Screening endoscopy in 1988-87 appeared to provide strong protection against distal stage C&D cancers (age-adjusted RR=0.16, CI=0.02-1.23) but no protection against proximal stage C&D cancers (age-adjusted RR=0.96, CI=0.32-2.91). Conclusions: This study provides strong evidence for a protective effect of screening sigmoidoscopy on colorectal cancer incidence and mortality and supports recommendations for screening sigmoidoscopy as an approach to colon cancer prevention.     

Vitamins B2, B6, and B12 and risk of new colorectal adenomas in a randomized trial of aspirin use and folic acid supplementation

BACKGROUND: Folate, other vitamin B cofactors, and genes involved in folate-mediated one-carbon metabolism all may play important roles in colorectal neoplasia. In this study, we examined the associations between dietary and circulating plasma levels of vitamins B(2), B(6), and B(12) and risk colorectal adenomas. METHODS: The Aspirin/Folate Polyp Prevention Study is a randomized clinical trial of folic acid supplementation and incidence of new colorectal adenomas in individuals with a history of adenomas (n = 1,084). Diet and supplement use were ascertained through a food frequency questionnaire administered at baseline. Blood collected at baseline was used to determine plasma B-vitamin levels. We used generalized linear regression to estimate risk ratios (RR) and 95% confidence intervals (95% CI) as measures of association. RESULTS: We found a borderline significant inverse association with plasma B(6) [pyridoxal 5'-phosphate (PLP)] and adenoma risk (adjusted RR Q4 versus Q1, 0.78; 95% CI, 0.61-1.00; P(trend) = 0.08). This association was not modified by folic acid supplementation or plasma folate. However, the protective association of PLP with adenoma risk was observed only among subjects who did not drink alcohol (P(interaction) = 0.03). Plasma B(2) (riboflavin) was inversely associated with risk of advanced lesions (adjusted RR Q4 versus Q1, 0.51; 95% CI, 0.26-0.99; P(trend) = 0.12). No significant associations were observed between adenoma risk and plasma vitamin B(12) or dietary intake of vitamin B(2) and B(6). When we examined specific gene-B-vitamin interactions, we observed a possible interaction between methylenetetrahydrofolate reductase -C677T and plasma B(2) on risk of all adenomas. CONCLUSION: Our results suggest that high levels of PLP and B(2) may protect against colorectal adenomas.     

Reproductive factors related to the risk of colorectal cancer by subsite: a case-control analysis

The authors hypothesized that reproductive factors of colorectal cancer, which are probably mediated by endogenous hormones, would differ according to colonic subsite. Information on reproductive factors was obtained from 372 female colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and 31,061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between 1988 and 1995. Multiple logistic analysis showed that late age at interview, family history of colorectal cancer among first-degree relatives, menstrual regularity, late age at menopause, late age at first pregnancy and late age at first full-term pregnancy were significantly associated with the risk of colorectal cancer. None of the risk factors were significantly dissociated between colon and rectal cancer. In polytomous logistic regression analysis, particularly noteworthy was the fact that the odds ratios for age at menarche (P-value for heterogeneity of odds ratios = 0.010), age at first pregnancy (P = 0.016) and age at first full-term pregnancy (P = 0.028) were significantly higher for distal than for proximal colon cancer. This study supports the hypotheses that there might be an association between reproductive factors and risk of colon cancer, and that the carcinogenesis of colon cancer, by subsite, might show aetiologic distinctions.     

A follow-up study of physical activity and incidence of colorectal polyps in African-American women.

BACKGROUND: Physical activity is associated with a reduced risk of colon cancer, but the effect of activity on colorectal adenomas, which are precursors to colon cancer, is uncertain. The influence of physical activity on colorectal adenomas among African-American women is of particular interest because African-American women have an increased risk of colon cancer relative to other U.S. women. METHODS: We prospectively assessed the relation of physical activity to the incidence of colorectal polyps among African-American women. We followed 45,400 women in the Black Women's Health Study from 1997 to 2003. Data were obtained by biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390 women reported having been diagnosed with colorectal polyps. A review of medical records of 58 women who reported colorectal polyps indicated that 59% had adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous exercise and hours per week of walking to metabolic equivalent (MET)-hours. We estimated incidence rate ratios with Cox proportional hazard models, controlling for age, body mass index, smoking, family history of colorectal cancer, and education. RESULTS: For total MET-hours/wk spent in walking and vigorous exercise, the incidence rate ratio decreased from 0.94 for <5 MET-hours/wk to 0.72 for >or=40 MET-hours/wk (P(trend) = 0.01). The inverse association was apparent among most subgroups examined, including women who may be at higher risk of colorectal adenomas because of being obese. CONCLUSIONS: Increased physical activity is associated with a reduced incidence of colorectal polyps among African-American women.     

A prospective study of reproductive and menstrual factors and colon cancer risk in Japanese women: findings from the JACC study

The effects of reproductive factors on the etiology of colon cancer in Asian populations remain unexplored. So we examined 38,420 Japanese women aged 40-79 years who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During an average 7.6 years of follow-up, we documented 207 incident colon cancers. Multivariate analysis indicated that colon cancer risk was likely to be lower among parous women than among nulliparous. Women who had two abortions or more had a 72% higher risk of developing colon cancer [relative risk (RR) 1.72; 95% confidence interval (CI) 1.16-2.55; trend P < 0.01] compared with women who never had an abortion. The RR of colon cancer among postmenopausal women significantly decreased with increasing age at menarche (trend P = 0.01). No apparent association between colon cancer and gravida, age at first birth, age at menopause, or duration of menstruation was seen. These prospective data support the hypothesis that female reproductive events modify colon cancer risk, and suggest that reproductive factors, particularly age at menarche and having an abortion, may be of importance in the etiology of colon cancer among Japanese women.     

A Case-Control Study of Male Colorectal Cancer in Aichi Prefecture, Japan: with Special Reference to Occupational Activity Level, Drinking Habits and Family History

The relationships of occupational activity level, drinking habits and family history of cancer to the risk of male colorectal cancer by subsites were investigated in a case-control study involving 1,716 cases with colon cancer, 1,611 cases with rectal cancer and 16,600 controls with other sites of cancer identified from the Aichi Cancer Registry, Japan 1979–1987. An occupation with a low activity level was associated with an increased risk of colorectal cancer; the age-adjusted relative risk (RR) compared to the high activity level group was 1.92 (95% confidence interval (CI): 1.38–2.67) for proximal colon cancer, 1.52 (95% CI: 1.19–1.94) for distal colon cancer and 1.38 (95% CI: 1.17–1.62) for rectal cancer. Beer drinkers showed an increased risk of colorectal cancer; the age-adjusted RR was 1.49 (95% CI: 1.13–1.95) for proximal colon cancer, 1.65 (95% CI: 1.34-2.04) for distal colon cancer and 1.88 (95% CI: 1.62–2.18) for rectal cancer. The RR for family history of colorectal cancer was 3.40 (95% CI: 2.19–5.29) for proximal colon cancer, 2.54 (95% CI: 1.73–3.75) for distal colon cancer and 1.78 (95% CI: 1.28–2.49) for rectal cancer. Multivariate analysis controlled for age, residence, marital status and smoking in addition to occupational activity level, beer drinking and family history of colorectal cancer did not materially change the RRs. When these three variables were combined, the RR was 15.72 (95% CI: 5.40–45.78) for proximal colon cancer, 10.55 (95% CI: 4.24–26.27) for distal colon cancer and 6.69 (95% CI: 3.12–14.36) for rectal cancer.     

GSTM1, GSTT1, and GSTP1 polymorphisms and risk of advanced colorectal adenoma.

Cigarette smoking is a risk factor for colon adenoma. The glutathione S-transferase enzymes are involved in the detoxification of carcinogenic compounds including those found in tobacco smoke, and thus, may be important modifiers of individual risk of developing this disease. We examined the prevalence of GSTM1 and GSTT1 gene deletions, and two GSTP1 polymorphisms in 772 cases with advanced colorectal adenomas (>1 cm, villous elements or high-grade dysplasia) of the distal colon (descending or sigmoid colon or rectum) and 777 sigmoidoscopy negative controls enrolled in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Epidemiologic data on smoking was collected by self-administered questionnaire and DNA was extracted from whole blood or buffy coat. For GSTM1 and GSTT1, we used a newly developed TaqMan-based assay capable of discriminating heterozygous (+/-) individuals from those with two active alleles (+/+) and homozygous deletions (-/-). For GSTP1, the I105V and the A114V substitutions were identified using end point 5' nuclease assays (TaqMan). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were determined using unconditional logistic regression, controlling for age, race, and gender. Advanced adenoma risk was increased in current/former smokers (OR, 1.4; 95% CI, 1.2-1.8). Risks were decreased in subjects with > or =1 inactive GSTM1 alleles (OR, 0.6; 95% CI, 0.4-0.9); and the association was independent of smoking status (P interaction = 0.59). Having > or =1 inactive GSTT1 allele was associated with increased risk among smokers (OR, 1.4; 95% CI, 1.1-1.9; P trend = 0.02) but not among never smokers (OR, 0.9; 95% CI, 0.6-1.3) and a significant interaction between smoking and genotype was observed (P interaction = 0.05). In summary, this is the first study to report associations between colorectal adenomas and GSTM1 wild-type and GSTT1 null allele among smokers. These findings only became apparent using a newly developed assay able to distinguish heterozygous from wild-type individuals. Our data provide evidence that phenotypic differences between these two groups exist.     

Reproductive factors and colon cancers

In Los Angeles County, the age-adjusted incidence rate of colon cancer in men is almost 30% higher than that in women; however, in the descending and sigmoid colon, age-specific incidence rates for women are higher than those for men before age 55. Since menstrual and/or reproductive factors may be involved in producing this crossover in age-specific rates, they were examined in a population-based case-control study involving 327 white women with adenocarcinoma of the colon and age-, race- and neighbourhood-matched controls. After adjustment for other factors associated with colon cancer in this study (family history of large bowel cancer, total fat intake, calcium, weight and activity level), ever having been pregnant was protective (RR = 0.56, 95% CI = 0.33-0.97). For one to two pregnancies, the RR was 0.76 (CI = 0.42-1.37); for three or more pregnancies, the RR was 0.45 (CI = 0.25-0.81). However, the relationship between the number of pregnancies and colon cancer risk was actually U-shaped, with risk decreasing with successive pregnancies up to four and then increasing with additional pregnancies. The U-shaped relationship was present for incomplete as well as for full-term pregnancies and was more striking for cancers occurring in the distal (descending and sigmoid) than proximal (caecum to splenic flexure) colon. Risk was not related to age at menarche or use of exogenous oestrogens, but delayed natural menopause was weakly protective in the proximal but not distal colon. The crossover in incidence rates in the distal colon can be completely accounted for by the pregnancy effect. The U-shape of the pregnancy curve suggests the possibility of competing factors, some protective, especially after one or several pregnancies, and others conferring increasing risk with successive pregnancies, regardless of the pregnancy outcome.