Relative Risk Of Colon Cancer Research Articles

Colorectal Cancer and Nonfermented Milk, Solid Cheese, and Fermented Milk Consumption: A Systematic Review and Meta-Analysis of Prospective Studies

Colorectal cancer is the second most prevalent cancer worldwide. A systematic review and meta-analysis of prospective studies was conducted to examine the association between intake of different types of dairy foods during adulthood and the development of colorectal cancer, specifically comparing nonfermented milk, solid cheese, and fermented milk. Seven databases were systematically searched and 15 cohort studies selected for inclusion, involving over 900,000 subjects and over 5200 colorectal cancer cases. Meta-analysis resulted in an overall relative risk of colon cancer of 0.74 (95% confidence interval 0.60–0.91) in men consuming nonfermented milk (highest intake category averaging 525 g/day). No association was found between consumption of nonfermented milk and rectal cancer in men or nonfermented milk and colon or rectal cancer in women. No protective association was found between consumption of solid cheese or fermented milk and colorectal cancer. Reasons for the differences in the impact of nonfermented milk, solid cheese, and fermented milk in the colon are discussed. This meta-analysis supports the inverse association between nonfermented milk consumption and risk of colon cancer in men, and provides an evidence base to assist in the formulation of dietary guidelines involving dairy foods.

Heme Iron from Meat and Risk of Colorectal Cancer: A Meta-analysis and a Review of the Mechanisms Involved

Red meat and processed meat intake is associated with a risk of colorectal cancer, a major cause of death in affluent countries. Epidemiological and experimental evidence supports the hypothesis that heme iron present in meat promotes colorectal cancer. This meta-analysis of prospective cohort studies of colon cancer reporting heme intake included 566,607 individuals and 4,734 cases of colon cancer. The relative risk of colon cancer was 1.18 (95% CI: 1.06-1.32) for subjects in the highest category of heme iron intake compared with those in the lowest category. Epidemiological data thus show a suggestive association between dietary heme and risk of colon cancer. The analysis of experimental studies in rats with chemically-induced colon cancer showed that dietary hemoglobin and red meat consistently promote aberrant crypt foci, a putative precancer lesion. The mechanism is not known, but heme iron has a catalytic effect on (i) the endogenous formation of carcinogenic N-nitroso compounds and (ii) the formation of cytotoxic and genotoxic aldehydes by lipoperoxidation. A review of evidence supporting these hypotheses suggests that both pathways are involved in heme iron toxicity.

Nutritional Targeting of Cyclooxygenase-2 for Colon Cancer Prevention

Factors related to diet and life style have been identified as primary determinants in about 80% of colorectal cancers. Non-steroidal anti-inflammatory drugs (NSAID) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIB) reduce the relative risk of colon cancer. To overcome systemic COX inhibition associated with NSAID and COXIB, there is a growing interest in developing alternative colon cancer prevention strategies using diet-based approaches that target COX-2. The transition from aberrant crypt foci (ACF) to colon cancer is a multiyear process providing opportunities for nutritional targeting of genes influencing the course of this disease process at early stages of development. The activation of the proinflammatory gene COX-2 and PG production in the colonic mucosa are recognized risk factors in colon cancer. Many natural food components may impact colon cancer risk by interfering with ligand-activated receptors, signal transduction pathways, and transcription factors involved in stimulation of COX-2 expression. In this review, we highlight key upstream features of signaling pathways and transcriptional control of the COX-2 gene and discuss opportunities for dietary modulation of COX-2 expression in gastro-intestinal cancers with special emphasis on prevention of colorectal tumors. Review of the experimental evidence suggests that dietary strategies based on specific or cocktails of bioactive food components as well nutritional-pharmacological combinations targeted to regulation of COX-2 expression and activity may prove useful in the prevention of colon cancer. An integrated approach may offer the advantage of combined higher efficacies. Future studies should investigate the efficacy of combinations of bioactive food compounds on epigenetic regulation of the COX-2 gene and characterize potential synergies and amplification effects resulting from the concomitant use of bioactive food components and COX-2 inhibitors.

Selenium, Folate, and Colon Cancer

Selenium is an essential trace element that has been implicated in cancer risk; however, study results have been inconsistent with regard to colon cancer. Our objectives were to 1) investigate the association between selenium and colon cancer, 2) evaluate possible effect measure modifiers, and 3) evaluate potential biases associated with the use of postdiagnostic serum selenium measures. The North Carolina Colon Cancer Study is a large population-based, case-control study of colon cancer in North Carolina between 1996 and 2000 (n = 1,691). Nurses interviewed patients about diet and lifestyle and drew blood specimens, which were used to measure serum selenium. Individuals who had both high serum selenium (> 140 mcg/l) and high reported folate (> 354 mcg/day) had a reduced relative risk of colon cancer [odds ratio (OR) = 0.5, 95% confidence interval (CI) = 0.4–0.8). The risk of colon cancer for those with high selenium and low folate was approximately equal to the risk among those with low selenium and low folate (OR = 1.1, 95% CI = 0.7–1.5) as was the risk for those with low selenium and high folate (OR = 0.9, 95% CI = 0.7–1.2). We did not find evidence of bias due to weight loss, stage at diagnosis, or time from diagnosis to selenium measurement. High levels of serum selenium and reported folate jointly were associated with a substantially reduced risk of colon cancer. Folate status should be taken into account when evaluating the relation between selenium and colon cancer in future studies. Importantly, weight loss, stage at diagnosis, or time from diagnosis to blood draw did not appear to produce strong bias in our study.

Folate and Vitamin B6 Intake and Risk of Colon Cancer in Relation to p53 Expression

Considerable evidence suggests that a low-folate diet increases the risk of colorectal cancer, although the results of a recent randomized trial indicate that folate supplementation may not reduce the risk of adenoma recurrence. In laboratory models, folate deficiency appears to induce p53 mutation. We immunohistochemically assayed p53 expression in paraffin-fixed colon cancer specimens in a large prospective cohort of women with 22 years of follow-up to examine the relationship of folate intake and intake of other one-carbon nutrients to risks by tumor p53 expression. A total of 399 incident colon cancers accessible for p53 expression were available. The effect of folate differed significantly according to p53 expression (P(heterogeneity) = .01). Compared with women reporting folate intake <200 microg/day, the multivariate relative risks (RRs) for p53-overexpressing (mutated) cancers were 0.54 (95% confidence interval [CI], 0.36-0.81) for women who consumed 200-299 microg/day, 0.42 (95% CI, 0.24-0.76) for women who consumed 300-399 microg/day, and 0.54 (95% CI, 0.35-0.83) for women who consumed >or=400 microg/day. In contrast, total folate intake had no influence on wild-type tumors (RR, 1.05; 95% CI, 0.73-1.51; comparing >or=400 with <200 microg/day). Similarly, high vitamin B(6) intake conferred a protective effect on p53-overexpressing cancers (top versus bottom quintile: RR, 0.57; 95% CI, 0.35-0.94; P(heterogeneity) = .01) but had no effect on p53 wild-type tumors. We found that low folate and vitamin B(6) intake was associated with an increased risk of p53-overexpressing colon cancers but not wild-type tumors.

Changing population characteristics, effect-measure modification, and cancer risk factor identification

Epidemiologic studies have identified a number of lifestyle factors, e.g. diet, obesity, and use of certain medications, which affect risk of colon cancer. However, the magnitude and significance of risk factor-disease associations differ among studies. We propose that population trends of changing prevalence of risk factors explains some of the variability between studies when factors that change prevalence also modify the effect of other risk factors. We used data collected from population-based control who were selected as study participants for two time periods, 1991–1994 and 1997–2000, along with data from the literature, to examine changes in the population prevalence of aspirin and non-steroidal anti-inflammatory medication (NSAID) use, obesity, and hormone replacement therapy (HRT) over time. Data from a population-based colon cancer case-control study were used to estimate effect-measurement modification among these factors. Sizeable changes in aspirin use, HRT use, and the proportion of the population that is obese were observed between the 1980s and 2000. Use of NSAIDs interacted with BMI and HRT; HRT use interacted with body mass index (BMI). We estimate that as the prevalence of NSAIDs use changed from 10% to almost 50%, the colon cancer relative risk associated with BMI >30 would change from 1.3 to 1.9 because of the modifying effect of NSAIDs. Similarly, the relative risk estimated for BMI would increase as the prevalence of use of HRT among post-menopausal women increased. In conclusion, as population characteristics change over time, these changes may have an influence on relative risk estimates for colon cancer for other exposures because of effect-measure modification. The impact of population changes on comparability between epidemiologic studies can be kept to a minimum if investigators assess exposure-disease associations within strata of other exposures, and present results in a manner that allows comparisons across studies. Effect-measure modification is an important component of data analysis that should be evaluated to obtain a complete understanding of disease etiology.

Body Mass and Colorectal Cancer Risk in the NIH-AARP Cohort

In most studies, body mass index (BMI) has been associated with increased risk of colorectal or colon cancer in men, but the relation is weaker and less consistent for women, possibly because of interactions with age or hormone replacement therapy. The authors examined the relation between BMI and colorectal cancer incidence in a large, prospective US cohort of 307,708 men and 209,436 women from the NIH-AARP Diet and Health Study. During follow-up of the cohort from 1995 to 2000, 2,314 cases of colorectal cancer were observed in men and 1,029 in women. BMI was related to increased risk of incident colon cancer, but not rectal cancer, for both men and women. For men, relative risks of colon cancer for a BMI of 18.5-<23, 23-<25, 25-<27.5, 27.5-<30, 30-<32.5, 32.5-<35, 35-<40, and > or = 40 kg/m(2) were 1.0 (referent), 1.11, 1.22, 1.44, 1.53, 1.57, 1.71, and 2.39, respectively (95% confidence interval: 1.59, 3.58; p-trend < 0.0005). Corresponding relative risks for women were 1.0, 1.20, 1.29, 1.31, 1.28, 1.13, 1.46, and 1.49 (95% confidence interval: 0.98, 2.25; p-trend = 0.02). BMI was related to colon cancer risk for younger (aged 50-66 years) but not older (aged 67-71 years) women. The association was not modified by hormone replacement therapy in women or physical activity in men or women.

Associations between ERα, ERβ, and AR Genotypes and Colon and Rectal Cancer

Estrogen and androgens are thought to be involved in the etiology of colorectal cancer. We evaluate genetic variants of the estrogen receptor genes (ERalpha and ERbeta) and the androgen receptor gene (AR). We use data from two large case-control studies of colon (n = 1,580 cases and 1,968 controls) and rectal (n = 797 cases and 1,016 controls) cancer. We evaluated the 351A >G XbaI polymorphism of ERalpha, the 1,082 G >A and CA repeat polymorphisms of ERbeta, and the CAG repeat of AR. Having two 25 or more CA repeats in ERbeta was associated with an increased relative risk of colon cancer in women [odds ratio (OR), 2.13; 95% confidence interval (95% CI), 1.24-3.64] but not in men (P(interaction) relative excess risk from interaction < 0.01; multiplicative = 0.03). Increasing number of AR CAG repeats was directly associated with colon cancer among men (OR, 1.28; 95% CI, 1.06-1.54), but not women (OR, 0.83; 95% CI, 0.68-1.02); the interaction P value for AR gene x sex was <0.01. Taking hormone replacement therapy (HRT) was associated with a reduced risk of colon cancer in the presence of the R allele of the ERbeta gene, whereas an R allele was associated with increased risk among postmenopausal women who did not take HRT. Postmenopausal women not using HRT who had > or =25 CA repeats of the ERbeta gene had over a 6-fold increased risk of colon cancer (OR, 6.71; 95% CI, 2.89-15.6). Our results suggest that the ERbeta gene is more important than ERalpha in the etiology of colorectal cancer.

Family history assessment to detect increased risk for colorectal cancer: conceptual considerations and a preliminary economic analysis.

Although the rationale for earlier screening of persons with a family history of colorectal cancer is plausible, there is no direct evidence that earlier assessment is either effective or cost-effective. To estimate the clinical and economic effect of using family history assessment to identify persons for colorectal cancer screening before age 50. We developed a decision model to compare costs and outcomes for two scenarios: (a) standard population screening starting at age 50; (b) family history assessment at age 40, followed by screening colonoscopy at age 40 for those with a suggestive family history of colorectal cancer. The analysis was conducted using the health insurer perspective. Using U.S. population estimates, 22 million would be eligible for family history assessment, and one million would be eligible for early colonoscopy; 2,834 invasive cancers would be detected, and 29,331 life years would be gained. The initial program cost would be USD $900 million. The discounted cost per life year gained of family history assessment versus no assessment equals USD $58,228. The results were most sensitive to the life expectancy benefit from earlier screening, the cost of colonoscopy, and the relative risk of colon cancer in those with a family history. The cost-effectiveness of family history assessment for colorectal cancer approaches that of other widely accepted technologies; yet, the results are sensitive to several assumptions where better data are needed. Because of the relatively high prevalence of family history in the population, careful analysis and empirical data are needed.

Height and Body Mass Index in Relation to Colorectal and Gallbladder Cancer in Two Million Norwegian Men and Women

The present study aimed at exploring the relations between BMI and stature and colorectal and gallbladder cancer in a huge Norwegian cohort with measured height and weight. Height and weight were measured in two million Norwegian men and women aged 20-74 during 1963-2001. During follow-up, 47,117 colorectal and 1715 gallbladder cancer cases were registered. Relative risks (RRs) of colorectal and gallbladder cancer were estimated using Cox proportional hazards regression. The risk of colon cancer increased with increasing BMI in men; the RR of colon cancer per unit increase in BMI was 1.04 (95% CI: 1.04-1.05). For mucinous colorectal adenocarcinomas, the risk increased to a larger extent with increasing BMI in both sexes. The RR of colorectal cancer associated with 10 cm increase in height was 1.14 (95% CI: 1.11-1.16) in men and 1.17 (95% CI: 1.14-1.20) in women. The risk of gallbladder cancer increased with increasing BMI in women; the overall RR associated with one unit increase in BMI was 1.06 (95% CI: 1.04-1.07). There was no association between height and gallbladder cancer in either sex. The risk of colon cancer increased with increasing BMI in men, and the risk of gallbladder cancer increased with increasing BMI in women. In both sexes, the risk of colon cancer increased with increasing height.

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 prospective study on the possible association between having children and colon cancer risk: Findings from the JACC Study

If having children is regarded as an exposure in life, its effect on a host could be considered as being due to female sex hormones associated with pregnancy in women and some lifestyle factors associated with large families in both men and women. To explore the roles of having children in the etiology of colon cancer, we examined 36,629 women and 24,877 men aged 40-79 years who completed a questionnaire on the number of children and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During 291,080 and 200,648 person-years of follow-up, we documented 198 female and 202 male incident colon cancers, respectively. After adjusting for some factors known or suspected to modify the risk of colon cancer, compared with the women with no children, the multivariate-adjusted relative risks of colon cancer were 0.74 (95% confidence interval [CI]: 0.30-1.84) for one child, 1.00 (95% CI: 0.46-2.20) for two, 0.70 (95% CI: 0.31-1.55) for three, and 0.59 (95% CI: 0.26-1.33) for four or more. The risk of colon cancer showed a significantly monotonic decrease with increasing number of children (P value for trend = 0.047). There was no association between the number of children and colon cancer risk among men. From these prospective data, having children may reduce risk of colon cancer among women, but not among men, suggesting that modifications of hormone profiles secondary to pregnancies may influence female colon cancer risk.

COX-2 and colorectal cancer.

Metabolites of arachidonic acid participate in normal growth responses and in aberrant cellular growth and proliferation, including carcinogenesis. The key step in the conversion of free arachidonic acid to prostaglandins is catalyzed by the cyclooxygenase enzyme (COX). There are two COX enzymes, COX-1 and COX-2. COX-1 is expressed constitutively and is part of normal cell metabolic functions. COX-2, on the other hand, is induced and expressed in neoplastic growths. The connection between COX expression and carcinogenesis was first implicated in studies that demonstrated the efficacy of aspirin and non-steroidal anti-inflammatory drugs to reduce the relative risk of colon cancer and also promote tumor regression in both humans and animal models of colon cancer. Investigation of the molecular basis of these observations showed that high levels of COX-2 protein were present in both human and animal colorectal tumors. A variety of evidence gathered from epidemiological, whole animal, and cellular studies indicate that unregulated COX-2 expression is a rate-limiting step in tumorigenesis and also that the loss of regulation occurs early in carcinogenesis. The interest in the COX-2 enzyme is that specific inhibition of COX-2 could theoretically avoid the gastrointestinal and other complications observed with the use of nonspecific COX inhibitors (most NSAIDs) or COX-1 inhibitors. The mechanisms by which COX-2 inhibitors lead to decreased colon carcinogenesis are not fully understood but they involve an increase not only in COX-2 dependent but also in COX-2 independent mechanisms.

Exercise and gastrointestinal function and disease: an evidence-based review of risks and benefits

Background & Aims : Exercise is beneficial to health because it reduces the risk of cardiovascular and endocrine diseases, improves bone and muscle conditioning, and lessens anxiety and depression. However, the impact of exercise on the gastrointestinal system has been conflicting. This systematic literature review evaluates the effect of the different modes and intensity levels of exercise on gastrointestinal function and disease using an evidence-based approach. Although more applicable to trained athletes and individuals who are highly active and, as such, at risk to experience the side-effects of exercise, an effort was made to state the level or degree of exercise or the lack of such evidence. Results : Light and moderate exercise is well tolerated and can benefit patients with inflammatory bowel disease and liver disease. Physical activity can also improve gastric emptying and lower the relative risk of colon cancer in most populations. Severe, exhaustive exercise, however, inhibits gastric emptying, interferes with gastrointestinal absorption, and causes many gastrointestinal symptoms, most notably gastrointestinal bleeding. Conclusions : This knowledge will enable physicians to prescribe physical exercise in health and disease and to better manage patients with exercise-related gastrointestinal disorders. Our understanding of exercise and its gastrointestinal manifestations as well as risks and benefits warrants further investigation.

Major Dietary Patterns and the Risk of Colorectal Cancer in Women

Several foods and nutrients have been implicated in the development of colon and rectal cancers. In this study, we prospectively assessed the associations between major dietary patterns and the risks of these 2 cancers in women. Using dietary information collected in 1984, 1986, 1990, and 1994 from 76 402 women aged 38 to 63 years without a history of cancer in 1984, we conducted factor analysis and identified 2 major dietary patterns: "prudent" and "Western." We calculated factor scores for each participant and examined prospectively the associations between dietary patterns and colon and rectal cancer risks. The prudent pattern was characterized by higher intakes of fruits, vegetables, legumes, fish, poultry, and whole grains, while the Western pattern, by higher intakes of red and processed meats, sweets and desserts, french fries, and refined grains. During 12 years of follow-up, we identified 445 cases of colon cancer and 101 cases of rectal cancer. After adjusting for potential confounders, we observed a relative risk for colon cancer of 1.46 (95% confidence interval, 0.97-2.19) when comparing the highest with the lowest quintiles of the Western pattern (P value for trend across quintiles, .02). The prudent pattern had a nonsignificant inverse association with colon cancer (relative risk for fifth quintile compared with the first, 0.71; 95% confidence interval, 0.50-1.00; P for trend across quintiles, .31). We did not observe any significant association between dietary patterns and rectal cancer. We found a significant positive association between the Western dietary pattern and the risk of colon cancer.

Folate Status: Effects on Pathways of Colorectal Carcinogenesis

Many epidemiologic, animal and human studies suggest that folate status modulates carcinogenesis. Although these observations have been made in a number of tissues, the data are clearly most compelling for the colorectum. The mechanism(s) by which this modulation is mediated remains ill defined. Alterations in either genome-wide or gene-specific DNA methylation and/or alterations in DNA stability, resulting from DNA strand breaks or uracil misincorporation, are leading candidates in this regard. Folate has a central role in biological methylation and nucleotide synthesis, and therefore it is not surprising that folate depletion has been observed to alter DNA methylation and diminish DNA stability. The hypothesis that these two pathways are the means by which folate modulates cancer risk is also supported by the epidemiological observation that a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR; EC 1.5.1.20) gene differentially affects the relative risk of colon cancer depending on folate status, because MTHFR catalyzes the reaction that determines whether cellular folate is diverted into biological methylation or nucleotide synthesis. This phenomenon suggests that it is an imbalance between biological methylation and nucleotide synthesis that is responsible for folate-related carcinogenesis. The control of cell proliferation, which also is related to DNA methylation, is another candidate mechanism by which folate status modulates carcinogenesis. In cell culture studies, folate supplementation has been observed to suppress excessive cell proliferation. Understanding the mechanisms by which folate status modulates carcinogenesis is important for advancing insight into cancer biology and for facilitating those efforts to translate research in folate and carcinogenesis into effective and safe public health initiatives.

Tea consumption and the reduced risk of colon cancer -- results from a national prospective cohort study.

This study examines the relationship between tea consumption and colon cancer risk in the US population. Data from the NHANES I Epidemiologic Follow-up study (NHEFS) were used to examine the hypothesis. Cox proportional hazard models were used to examine the hypothesis of a protective effect of frequent tea consumption on colon cancer occurrence. Due to differences in the precision of the exposure data, we analysed two cohort periods based on the NHEFS. Cohort I was based on the survey conducted at the NHEFS baseline and Cohort II began at the first follow-up. After excluding non-incidence cases and cases lost to follow-ups, there were 2359 tea users and 6498 non-tea users at baseline and 7656 tea users and 4514 non-tea users at the first follow-up. : After adjusting for confounders, the relative risks of colon cancer are 0.57 (95% confidence interval (CI) 0.42, 0.78) and 0.59 (95% 1.00) for subjects who consumed <or=1.5 cups and >1.5 cups per day, respectively, compared with non-tea users in Cohort II. Although more women consumed tea and the mean intake was higher, the preventive effect of tea consumption on colon cancer was found predominantly in men. The relative risks of colon cancer are 0.41 (95% 0.66) for men who consumed <or=1.5 cups day-1 and 0.30 (95% 0.98) for >1.5 cups day-1 of tea consumption (P-value for trend <0.01). No significant results were found in Cohort I. This study suggests an inverse association between colon cancer risk and habitual tea consumption.

Cyclooxygenase-2 expression in Barrett's esophagus.

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus.

Leisure-time physical activity, body size, and colon cancer in women. Nurses' Health Study Research Group.

Physical inactivity and high body mass index (weight in kilograms divided by height in square meters) have been linked to increased risk of colon cancer. However, none of the few prospective studies in women has shown a statistically significant reduction in colon cancer incidence or mortality associated with increased leisure-time physical activity. In this prospective study, we asked whether leisure-time physical activity, body mass index, or body fat distribution could significantly influence the risk of colon cancer in women. The participants in this study were enrolled in the Nurses' Health Study, which began in 1976. Every 2 years, the women provided additional personal information and information on medical risk factors and major medical events. The time spent per week at a variety of leisure-time physical activities was determined, and the time spent at each activity was multiplied by its typical energy expenditure, expressed in terms of metabolic equivalents or METs. The resulting values for each woman were added to yield an MET-hours-per-week score. Reported diagnoses of colon cancer were confirmed by review of hospital records and pathology reports. Relative risks and associated 95% confidence intervals were calculated. In multivariate analyses that included body mass index, women who expended more than 21 MET-hours per week on leisure-time physical activity had a relative risk of colon cancer of 0.54 (95% confidence interval [CI] = 0.33-0.90) in comparison with women who expended less than 2 MET-hours per week. Women who had a body mass index greater than 29 kg/m2 had a relative risk of colon cancer of 1.45 (95% CI = 1.02-2.07) in comparison with women who had a body mass index less than 21 kg/m2. A tendency toward higher colon cancer risk was observed for increasing waist-to-hip ratio (relative risk = 1.48 [95% CI = 0.88-2.49] for comparison of the highest quintile ratio [>0.833] to the lowest [<0.728]). The significant inverse association between leisure-time physical activity and incidence of colon cancer in women in this study is consistent with what has been found in men. Recommendations to increase physical activity and maintain lean body weight should receive greater emphasis as part of a feasible approach to the prevention of colon cancer.

Colorectal cancer incidence among atomic bomb survivors, 1950-80.

Colorectal cancer incidence in the LSS sample during 1950-80 was investigated. A total of 730 incidence cases of colorectal cancer were confirmed from a variety of sources. Sixty-two percent of the cancers were microscopically verified and 12% were ascertained through death certificate only. The risk of colon cancer increased significantly with intestinal dose, but no definite increase of risk was observed for rectal cancer. Relative risk at 1 Sv and excess risk per 10(4) PY-Sv for colon cancer are 1.80 (90% confidence internal 1.37-2.36) and 0.36 (90% confidence interval 0.06-0.77) respectively. City and sex did not significantly modify the dose-response of colon cancer, but the risk decreased with age at the time of bombings (ATB). The relative risk of colon cancer does not vary substantially over time following exposure. A non-linear dose response did not significantly improve the fit. Further, the anatomic location of the tumors indicate that the cecum and ascending, transverse and descending, and sigmoid colon seem equally sensitive to radiation. No difference in the distribution of tumor histological types could be observed by radiation dose.