A prospective study of intakes of zinc and heme iron and colorectal cancer risk in men and women

Although laboratory studies linked zinc and heme iron to colorectal cancer, epidemiologic evidence is limited. We prospectively examined these associations in the Nurses’ Health Study and Health Professionals Follow-up Study. We used Cox proportional hazards regression analyses to calculate cohort-specific relative risks (RRs) and pooled results using a fixed-effects model. We documented 2,114 incident colorectal cancer cases during up to 22 years of follow-up. Compared highest to lowest quintile of dietary zinc intake, the pooled multivariable RRs (95% CIs) were 0.86 (0.73, 1.02) for colorectal cancer, 0.92 (0.76, 1.11) for colon cancer, and 0.68 (0.47, 0.99) for rectal cancer. The significant inverse association between dietary zinc intake and risk of rectal cancer was mainly driven by data in women, although the difference in the sex-specific results was not statistically significant. For the same comparison, the pooled multivariable RRs (95% CIs) for heme iron were 1.10 (0.93, 1.30) for colorectal cancer, 1.06 (0.88, 1.29) for colon cancer, and 1.20 (0.83, 1.75) for rectal cancer. These associations were not significantly modified by alcohol consumption, body mass index, physical activity, menopausal status, or postmenopausal hormone use. Total zinc intake, total iron intake, dietary iron intake, and zinc or iron supplement uses were largely not associated with colorectal cancer risk. Our study does not support strong roles of zinc and heme iron intake in colorectal cancer risk; however, a suggestive inverse association of dietary zinc intake with rectal cancer risk in women requires further study.     

Macronutrients and colorectal cancer: a Swiss case-control study.

BACKGROUND: A role of energy and various nutrients, including protein, sugar, saturated and unsaturated fats, in colorectal cancer risk has been suggested, but should be better defined. PATIENTS AND METHODS: The association between dietary intake of various macronutrients and colorectal cancer risk was analysed using data from a case-control study conducted between 1992 and 2000 in the Swiss Canton of Vaud. The study comprised 286 case subjects (174 males, 112 females; median age 65 years) with incident, histologically confirmed colon (n = 149) or rectal (n = 137) cancer, and 550 control subjects (269 males, 281 females; median age 59 years) admitted to the same University Hospital for a wide spectrum of acute non-neoplastic conditions. Dietary habits were investigated using a validated food frequency questionnaire, including questions on 79 foods or recipes and on individual fat intake pattern. Multivariate odds ratios (OR) were obtained after allowance for age, sex, education, physical activity and energy intake. RESULTS: The risk of colon and rectal cancer increased with total energy intake (OR in highest and lowest tertile, 2.0 and 2.2, respectively). There was no significant relation with starches or proteins, a significant inverse relation with sugars (OR for the highest tertile, 0.5), a direct trend in risk of borderline significance for saturated fats (OR = 1.4 for the highest tertile), and significant inverse trends for monounsaturated (OR = 0.6) and polyunsaturated fats (OR = 0.6). CONCLUSIONS: These findings confirm that energy intake is directly related to colorectal cancer risk, and that different types of fat may have different roles in colorectal carcinogenesis.     

Fat and K-ras mutations in sporadic colorectal cancer in The Netherlands Cohort Study

Associations between dietary intake of various fats and specific K-ras mutations in colorectal cancer (CRC) were investigated within the framework of The Netherlands Cohort Study on diet and cancer (NLCS). After 7.3 years of follow-up and with exclusion of the first 2.3 years, 448 colon and 160 rectal cancer patients and 2948 subcohort members (55-69 years at baseline) were available for data-analyses. Mutation analysis of the K-ras gene was performed on all archival colon and rectal adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer cases and for K-ras mutation subgroups. The intake of total, saturated and monounsaturated fat was not significantly associated with colon or rectal cancer. High intake of dietary polyunsaturated fat and, specifically, linoleic acid is associated with an increased risk of mutated K-ras colon tumours. The RRs for 1 SD of increase of polyunsaturated fat and linoleic acid were 1.21 (95% CI 1.05-1.41) and 1.22 (95% CI 1.05-1.42), respectively, and similar associations were observed for both G > A transitions and G > T or G > C transversions in the colon. In contrast, no significant associations were observed with rectal cancer risk, overall nor with specific K-ras mutation status. A high intake of polyunsaturated fat, in particular linoleic acid, may be an important dietary risk factor for K-ras mutated colon tumours, possibly by generating G > A transitions or G > T or G > C transversions in the K-ras oncogene.     

Occupational physical activity and risk of cancer of the colon and rectum in New Zealand males

The association between occupational physical activity and risk of colorectal cancer by age and anatomic site was investigated in a study of 2,503 males with colorectal cancer registered with the New Zealand Cancer Registry during 1972–80. Occupational groups that involved high levels of physical activity or were predominantly sedentary were identified prior to analysis of the registry data. Relative to males in high physical activity occupations, males in sedentary occupations had an increased incidence of both cancer of the colon (relative risk [RR]=1.2; 95 percent confidence interval [CI]=1.0–1.4) and rectum (RR=1.3, CI=1.0–1.5). The RRs for sedentary workers were particularly elevated in the 35–44 and 45–54 year age-groups for colon cancer (RR=1.8 and 1.5, respectively) and in the 45–54 year age-group for rectal cancer (RR=1.5), whereas there was no increase in risk for sedentary workers in the 55–64 year age-group for either cancer site. The generalincrease in colon cancer incidence for New Zealand during the study period was reflected in the sedentary group, but there was no change in incidence among men in occupations involving high or intermediate levels of physical activity. There was no obvious pattern for the increased cancer risk for men in sedentary occupations by anatomic site. Current physiologic hypotheses for the effect of physical activity on colon cancer risk do not adequately explain an association of physical activity with risk of rectal cancer.Dr Fraser is affillated with the University of Otago, Medical School, Dunedin, New Zealand. Dr Pearce is with the Wellington School of Medicine, Wellington, New Zealand. Address correspondence to Dr Fraser, Department of Preventive and Social Medicine, University of Otago Medical School, PO Box 913, Dunedin, New Zealand.     

Cigarette and alcohol consumption and the risk of colorectal cancer in Shanghai, China.

The relation of cigarette smoking and alcohol drinking to colorectal cancer risk has been inconsistent in the epidemiological literature. In a population-based case-control study of colorectal cancer in Shanghai, China, where the incidence rates are rising sharply, we examined the association with tobacco and alcohol use. Cases were aged 30-74 years and newly diagnosed with cancers of the colon (N = 931) or rectum (N = 874) between 1990 and 1992. Controls (N = 1552) were randomly selected among Shanghai residents, frequency-matched to cases by gender and age. Information on lifetime consumption of tobacco and alcohol, as well as demographic and other risk factors, was obtained through in-person interviews. Associations with cigarette smoking and alcohol use were estimated by odds ratios (ORs) and 95% confidence intervals (CIs). Among women, the prevalence of smoking and alcohol drinking was low, and no significant association with colon or rectal cancer was observed. Although cigarette smoking among men was not related overall to colon or rectal cancer risk, there was a 50% excess risk of rectal cancer (OR 1.5, 95% CI 0.9-2.5) among those who smoked 55 or more pack-years. Among men, former alcohol drinkers had an increased risk of colon cancer (OR 2.3, 95% CI 1.4-3.7) but not rectal cancer, while current drinkers had a 30-50% excess risk of colon cancer only among those with long-term (30+ years) and heavy (>560 g ethanol/week) consumption. The excess risks were mainly associated with hard liquor consumption, with no material difference in risk between proximal and distal colon cancer. Although cigarette smoking and alcohol drinking in general were not risk factors for colorectal cancers in Shanghai, there were small excess risks for rectal cancer among heavy smokers and colon cancer among heavy drinkers.     

Methylenetetrahydrofolate reductase polymorphism, alcohol intake, and risks of colon and rectal cancers in Korea

Several, but not all, studies have reported that a variant genotype of the polymorphism (C677T) of 5,10-methylenetetrahydrofolate reductase (MTHFR), an enzyme in folate metabolism, is associated with a decreased risk of colorectal cancer. A case-control study was conducted to investigate the association of MTHFR polymorphism and heavy alcohol intake to colon and rectal cancer in Korean. Cases were a consecutive series of patients with histologically confirmed, incident colorectal cancer who were admitted to two university hospitals in Seoul, Korea between 1998 and 2000, and controls were selected at the same hospitals. A total of 243 cases (colon 111, rectum 132) and 225 controls were enrolled. While the genotype of MTHFR was not associated with the overall risk of colorectal cancer, increased colon cancer risk was found to be associated with the CT and TT genotypes combined (multivariate odds ratio [OR] 2.01, 95% confidence interval [CI] 1.14-3.53) compared with the wild type. The risk of rectal cancer was found to be, though statistically non-significant, lower in those with the CT and TT genotypes combined (multivariate OR 0.67, 95% CI: 0.43-1.07). Those consuming two or more drinks per day (30 g+/day) had nearly twice the colorectal cancer risk (multivariate OR 1.94, 95% CI 1.03-3.68) of light or non-drinkers (<5 g/day). The present study did not find a reduced risk of colorectal or rectal cancer among those with a variant genotype of the MTHFR polymorphism, but observed rather an increased risk of colon cancer, suggesting that the effects of the MTHFR genotype may differ in populations with different levels of folate intake.     

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.     

Diet and cancer of the colon and rectum: a case-control study

In 1979-81, 419 patients with incident cases of colon and rectal cancer and 732 controls were questioned regarding diet and alcohol. Cancer cases were a population-based series reported to the South Australian Central Cancer Registry, were 30-74 years of age, and were residing in Metropolitan Adelaide. Controls were selected from the electoral roll and individually age- and sex-matched to cancer cases. The most consistent risk factor for colorectal cancer was dietary protein, which was associated with a twofold-to-threefold relative risk for colon cancer and for rectal cancer in women for all levels of consumption above the base line (i.e., the lowest consumption quintile). For male colon cancer the corresponding relative risk was similar; but for male rectal cancer, risk was elevated only at old ages. Total energy intake and, less clearly, meal frequency were also positively associated with increased risk. Total alcohol intake (but not specifically beer) was associated with increased risk of both colon and rectal cancer in women; in both sexes, there was an increased risk of colon and rectal cancer associated with spirits consumption. A reduced risk of rectal cancer was associated with vitamin C but not with vitamin A. The increased risk associated with high protein and total energy was confined to those consuming a low fiber diet, particularly among women; but some other aspects of the relationship between fiber consumption and risk of colorectal cancer were more complex. Some modifications and extensions of the current fat-to-bile acid-to-fiber theory of bowel carcinogenesis were suggested.     

Selected micronutrient intake and the risk of colorectal cancer.

The relationship between estimated intake of selected micronutrients and the risk of colorectal cancer was analysed using data from a case-control study conducted in northern Italy. The study was based on 828 patients with colon cancer, 498 with rectal cancer and 2,024 controls in hospital for acute, non-neoplastic, non-digestive tract diseases. Relative risks (RRs) of intake quintiles were computed after allowance for age, sex and other major potential confounding factors, including an estimate of total energy intake. No apparent trend in risk across intake quintiles was evident for retinol, vitamin D, methionine and calcium. For beta-carotene, ascorbic acid, vitamin E and folate there was a trend of a protective effect with increasing consumption: the RR for the highest versus the lowest quintile was 0.32 for beta-carotene, 0.40 for ascorbic acid, 0.60 for vitamin E and 0.52 for folate. These inverse associations were similar for colon and rectal cancer, and consistent across strata of sex and age. When simultaneous allowance was made for all these micronutrients, besides other covariates, the only persistent protective effects were for beta-carotene (RR = 0.38 for the highest quintile) and ascorbic acid (RR = 0.52). Whether this reflects a specific, or stronger, effect of these micronutrients, rather than problems of collinearity between micronutrients or other limitations of the data, remains open to discussion. Still, this study suggests that specific micronutrients may exert an independent protective effect against colorectal carcinogenesis.     

Dietary fiber and risk of colorectal cancer in the Japan collaborative cohort study.

To examine the association of dietary fiber with the risk of colorectal cancer in a population with a high incidence of cancer and a low fiber intake, we analyzed the data from the Japan Collaborative Cohort Study. From 1988 to 1990, 43,115 men and women aged 40 to 79 years completed a questionnaire on dietary and other factors. Intake of dietary fiber was estimated using a food frequency questionnaire. Rate ratios (RR) were computed by fitting proportional hazards models. During the mean follow-up of 7.6 years, 443 colorectal cancer cases were recorded. In all participants, we found a decreasing trend in risk of colorectal cancer with increasing intake of total dietary fiber; the multivariate-adjusted RRs across quartiles were 1.00, 0.96 [95% confidence interval (95% CI), 0.72-1.27], 0.72 (0.53-0.99), and 0.73 (0.51-1.03; P(trend) = 0.028). This trend was exclusively detected for colon cancer: the corresponding RRs were 1.00, 0.90 (95% CI, 0.64-1.26), 0.56 (0.38-0.83), and 0.58 (0.38-0.88; P(trend) = 0.002). The decrease in RRs with increasing intake of dietary fiber was larger in men than in women. No material differences appeared in the strength of associations with the risk between water-soluble and insoluble dietary fiber. For food sources of fiber, bean fiber intake was somewhat inversely correlated with colorectal cancer risk. This prospective study supported potential protective effects of dietary fiber against colorectal cancer, mainly against colon cancer. The role of dietary fiber in the prevention of colorectal cancer seems to remain inconsistent, and further investigations in various populations are warranted. (     

Associations between 5,10-methylenetetrahydrofolate reductase codon 677 and 1298 genetic polymorphisms and environmental factors with reference to susceptibility to colorectal cancer: a case-control study in an Indian population

Although the incidence rate of colorectal cancer is very low, and rectal cancer remains more common in India, a significant increase in its incidence has been reported for both men and women over the last 2 decades. We evaluated MTHFR genetic susceptibility and common environmental risk factors in the development of colon and rectal cancer, and assessed the interactions between gene and environmental factors with colorectal cancer in a case-control study in the Indian population. The study included 59 colon cancer cases, 243 rectal cancer cases and 291 controls. The variant MTHFR 677T allele is rare, while the 1298C allele is common among Indians. MTHFR 677T showed no association with colon cancer (OR = 0.82; 95% CI 0.28-2.05) and a nonstatistically significantly elevated risk with rectal cancer (OR = 1.51; 95% CI 0.86-2.68), and MTHFR 1298 CC genotype was found to be associated with a significantly decreased risk for both colon cancer (OR = 0.30, 95% CI 0.09-0.81) and rectal cancer (OR = 0.43, 95% CI 0.23-0.80). High intake of nonfried vegetables or fruits was inversely associated with both colon and rectal cancer risk. Especially, the combination of a high intake of nonfried vegetables and MTHFR 1298CC genotype was associated with the lowest rectal cancer risk (OR = 0.22, 95% CI 0.09-0.52). Regarding alcohol consumption, indigenous Indian alcohol drinkers (OR = 2.26, 95% CI 0.86-6.36), and those consuming alcohol for duration more than 20 years (OR = 1.55, 95% CI 0.73-3.33), were at a somewhat higher rectal cancer risk. Moreover, the consumed alcohol amount (gram-years) may be also associated with colon or rectal cancer risk.     

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.     

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.     

Meal frequency and risk of colorectal cancer.

The relation between meal frequency and the risk of colorectal cancer was investigated in a case-control study conducted in North Italy on 889 cases of colon cancer, 581 cases of rectal cancer, and 2475 controls admitted to hospital for acute, nonneoplastic, or digestive disorders. As compared to individuals who reported 2 or fewer meals per day, the multivariate colon cancer odds ratios were 1.7 [95% confidence interval (95% CI), 1.5-2.1] for 3, and 1.9 (95% CI, 1.1-3.3) for 4 meals or more. Corresponding rectal cancer odds ratios were 1.4 (95% CI, 1.1-1.7) for 3, and 1.9 (95% CI, 1.1-3.5) for 4 meals or more. The direct trends in risk of colorectal cancer with frequency of eating were not substantially modified by allowance for various dietary and nondietary potential confounding factors, including an approximate measure of total energy intake, and did not show significant effect modification across strata of age, sex, education, and other major risk covariates. A role of meal frequency in the etiology of colorectal cancer is biologically plausible, since when a meal is eaten, the gallbladder contracts and releases bile acids. Thus, eating patterns can influence the enterohepatic circulation and, consequently, the exposure time of intestinal mucosa to bile acids.     

Alcohol intake and colorectal cancer risk: a dose-response meta-analysis of published cohort studies

The epidemiologic evidence support that alcohol intake might be associated with increased colorectal cancer risk. However, the results by anatomic site in the large bowel are inconsistent. We conducted a meta-analysis of prospective cohort studies published between 1990 and June 2005 on the relationship between alcohol intake and colon and rectal cancer. We quantified associations with colon and rectal cancer using meta-analysis of relative risk (RR) associated to the highest versus the lowest category of alcohol intake and meta-analysis of study-specific dose-response slopes using fixed or random effect models depending on the heterogeneity of effects among studies. Sixteen prospective cohort studies including more than 6,300 patients with colorectal cancer were eligible for inclusion. High alcohol intake was significantly associated with increased risk of colon (RR = 1.50; 95% CI = 1.25, 1.79) and rectal cancer (RR = 1.63; 95% CI = 1.35, 1.97) when comparing the highest with the lowest category of alcohol intake, equivalent to a 15% increase of risk of colon or rectal cancer for an increase of 100 g of alcohol intake per week. The relationship did not differ significantly by anatomical site (colon, rectum). Using meta-regression analysis, we identified geographical area where the study was conducted as a possible source of between-study heterogeneity of effects among studies. Lifestyle recommendations for prevention of colorectal cancer should consider limiting alcohol intake.     

Food groups and risk of colorectal cancer in Italy

The proportion of colorectal cancer attributed to dietary habits is high, but several inconsistencies remain, especially with respect to the influence of some food groups. To further elucidate the role of dietary habits, 1,225 subjects with cancer of the colon, 728 with cancer of the rectum and 4,154 controls, hospitalized with acute non-neoplastic diseases, were interviewed between 1992 and 1996 in 6 different Italian areas. The validated food-frequency questionnaire included 79 questions on food items and recipes, categorised into 16 food groups. After allowance for non-dietary confounding factors and total energy intake, significant trends of increasing risk of colorectal cancer with increasing intake emerged for bread and cereal dishes (odds ratio [OR] in highest vs. lowest quintile = 1.7), potatoes (OR = 1.2), cakes and desserts (OR = 1.1), and refined sugar (OR = 1.4). Intakes of fish (OR = 0.7), raw and cooked vegetables (OR = 0.6 for both) and fruit other than citrus fruit (OR = 0.7) showed a negative association with risk. Consumption of eggs and meat (white, red or processed meats) seemed uninfluential. Most findings were similar for colon and rectum, but some negative associations (i.e., coffee and tea, and fish) appeared stronger for colon cancer. Our findings lead us to reconsider the role of starchy foods and refined sugar in light of recent knowledge on the digestive physiology of carbohydrates and the insulin/colon cancer hypothesis. The beneficial role of most vegetables is confirmed, with more than 20% reduction in risk of colorectal cancer from the addition of one daily serving. Int. J. Cancer 72:56–61, 1997. © 1997 Wiley-Liss Inc.     

Nutritional factors in colorectal cancer risk: a case-control study in Majorca.

The relationship between energy intake, selected nutrients and colorectal cancer was investigated in the population of Majorca, a Spanish island in the Mediterranean basin. A population-based case-control study using food frequency questionnaires was conducted during the period 1984-1988 and included 286 cases of colorectal cancer, 295 population controls and 203 hospital controls. Food composition tables and ad-hoc estimates of portion sizes were used to derive intake estimates of 29 nutrients and of total calories. Relative risks were calculated for quartiles of consumption of each specific nutrient after adjustment for total calorie intake. Colorectal cancer was found associated with dietary intake of total calories (RRs = 1.0, 1.6, 1.6, 2.6) and cholesterol (RRs = 1.0, 0.9, 1.7, 1.7) and a protective effect was associated with the intake of fibre from legumes (pulses) and folic acid. The associations and the trends were statistically significant. Among the main energy-supplying nutrients, after adjustment for calories from other sources, increased risks were found for protein (RRs = 1.0, 1.1, 1.7, 2.5), notably animal protein, and carbohydrates (RRs = 1.0, 1.5, 1.4, 2.2), whereas no effects were found for increased consumption of lipids or saturated fats.     

Associations between BMI,energy intake,energy expenditure, <Emphasis Type="Italic">VDR</Emphasis> genotype and colon and rectal cancers (United States)

Components of energy balance are important elements associated with colorectal cancer risk. In this study we examine the association between VDR genotypes, BMI, physical activity, and energy intake and risk of colorectal cancer. Data from a population-based case–control study of colon (1174 cases and 1174 controls) and rectal (785 cases and 1000 controls) cancer was used to evaluate the associations. The Bsm1, polyA, and Fok1 VDR polymorphisms were evaluated. For colon cancer, those who are obese were at greater risk of colon cancer if they had the SS or BB (OR=3.50; 95 CI=1.75–7.03; p interaction 0.03) or ff (OR=2.62; 95 CI=1.15–5.99; p interaction 0.12/) VDR genotypes. On the other hand, those who were least physically active were at greater risk of colon cancer if they had theff VDR genotype (OR=3.46; 95 CI=1.58–7.58; p interaction 0.05. The association between energy intake and colon cancer appears to be driven more by energy intake than Bsm1 or polyA VDR genotypes, although there was a significant interaction between the Fok1 VDR polymorphism and energy intake and risk of both colon and rectal cancer (p interaction 0.01 for colon and 0.04 for rectal). These data suggest a relationship between VDR genotype and factors related to energy balance in modifying colorectal cancer risk.     

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.     

Proanthocyanidins and the risk of colorectal cancer in Italy

Proanthocyanidins are a group of polymers of flavanols. Animal and in vitro studies suggest they decrease cancer risk, particularly of colorectal cancer. We used data from an Italian case–control study to investigate whether proanthocyanidins are related to colorectal cancer risk. Cases were 1,953 patients with incident, histologically confirmed colorectal cancer (1,225 colon cancers, 728 rectal cancers). Controls were 4,154 patients admitted for acute, non-neoplastic conditions. A reproducible and valid food frequency questionnaire was used. We estimated odds ratios (ORs) through multiple logistic regression models, including terms for potential confounding factors, and energy intake. A trend of decreasing risk with increasing intake of proanthocyanidins emerged for all classes except monomers. The OR for the highest vs. the lowest quintile of intake was 0.82 for monomers and dimers combined, 0.88 for monomers, 0.75 for dimers, 0.74 for all polymers with three or more mers, 0.84 for trimers, 0.80 for 4–6 mers, 0.79 for 7–10 mers, 0.69 for more than 10 mers, and 0.74 for total proanthocyanidins. The associations were apparently stronger for rectal than for colon cancer, in the absence of significant heterogeneity. These results may explain the protective effect of vegetables and fruit on colorectal cancer.