Intake of dietary folate vitamers and risk of colorectal carcinoma: results from The Netherlands Cohort Study

BACKGROUND: Several studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk. METHODS: The aim of the current study was to investigate the relationship between dietary folate intake and the risk of colorectal carcinoma in a large prospective cohort study in The Netherlands comprising 120,852 men and women aged 55-69 years. After 7.3 years of follow-up, 760 colon and 411 rectal carcinoma cases were available for analysis. Data processing and analysis used the case-cohort approach. A new Dutch database was used to estimate intakes of total and individual folate vitamers. RESULTS: Analyses adjusted for age, energy intake, family history of colorectal carcinoma, alcohol, vitamin C, iron, and dietary fiber intake yielded an inverse association between colon carcinoma risk and total dietary folate intake (rate ratio [RR]highest vs. lowest quintile, men: 0.73; 95% confidence interval [CI], 0.46-1.17, P trend = 0.03; women: 0.68; 95% CI, 0.39-1.20, P trend = 0.18). An inverse association between rectal carcinoma and total dietary folate intake was found only among men (RR highest vs. lowest quintile, men: 0.66; 95% CI, 0.35-1.21, P trend = 0.03). Analyses showed no clear difference in colorectal carcinoma risk associated with intake of different folate vitamers. CONCLUSIONS: Dietary folate intake was related inversely to colon and male rectal carcinoma risk.     

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. (     

Dietary patterns and subsequent colorectal cancer risk by subsite: a prospective cohort study

In order to investigate the associations between dietary patterns and the risk of colorectal cancer by subsite in Japan, the baseline data from a population-based cohort study of 20,300 men and 21,812 women were analyzed. We conducted factor analysis and identified 3 major dietary patterns, "healthy," "traditional" and "Western," and calculated the factor scores of each pattern for individuals. During 10 years of follow-up, 370 colorectal cancer cases were identified. We found a positive association between the traditional pattern and colon cancer risk in women [rate ratio for highest quartile (RR) = 2.06; 95% CI = 1.10-3.84; p for trend = 0.11], but not in men. This positive association was slightly stronger for proximal colon cancer (RR = 2.07; 95% CI = 0.84-5.12) than for distal colon cancer (RR = 1.84; 95% CI = 0.75-4.50). After multivariate adjustment, the Western dietary pattern was also positively associated with colon cancer risk in females (RR = 2.21; 95% CI = 1.10-4.45), with the strongest associations being observed for females with distal colon cancer (RR = 3.48; 95% CI = 1.25-9.65). We did not observe any significant association between the healthy dietary pattern and colon cancer risk. For rectal cancer, no significant associations were found for the 3 dietary patterns. In conclusion, we found that the traditional and the Western dietary patterns were positively associated with colon cancer risk in females.     

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re‐examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow‐up period of 16 years. In multivariable‐adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61–0.89 for highest vs. lowest quintile, p_trend = 0.0020 in men and HR = 0.76, 95% CI: 0.62–0.91, p_trend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74–0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59–0.95, p_trend = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (p_trend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal 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.     

Increased caffeine intake is associated with reduced risk of basal cell carcinoma of the skin

Studies in animals suggest that caffeine administration helps prevent squamous cell skin cancer development, but there have been limited epidemiologic studies on the association between caffeine consumption and skin cancer risk. Using data from the Nurses' Health Study and the Health Professionals Follow-up Study, we prospectively examined risks of basal cell carcinoma (BCC, 22,786 cases), squamous cell carcinoma (SCC, 1,953 cases), and melanoma (741 cases) in relation to caffeine intake. Cox proportional hazard models were used to calculate relative risks (RR) and 95% confidence intervals (CI). The amount of caffeine intake from all dietary sources was inversely associated with BCC risk. Compared with the lowest quintile, the highest quintile had the lowest risk (RR, 0.82 in women; 95% CI:,0.77-0.86 and RR, 0.87 in men; 95% CI, 0.81-0.94; Ptrend<0.0001 in both). A significant inverse association was also found between caffeinated coffee consumption and BCC risk. Compared with individuals who consumed caffeinated coffee less than 1 cup per month, women who consumed more than 3 cups/d had the lowest risk (RR, 0.79; 95% CI, 0.74-0.85; Ptrend<0.0001) and the RR for men was 0.90 (95% CI, 0.80-1.01; Ptrend=0.003). Caffeine from other dietary sources (tea, cola, and chocolate) was also inversely associated with BCC risk. Decaffeinated coffee consumption was not associated with a similar decrease in BCC risk. In contrast, caffeine intake was not found to be inversely associated with risks of SCC or melanoma. Our findings argue that caffeine intake in men and women is inversely associated with risk of BCC.     

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.     

Prospective study of colorectal cancer risk and physical activity, diabetes, blood glucose and BMI: exploring the hyperinsulinaemia hypothesis

A sedentary lifestyle, obesity, and a Westernized diet have been implicated in the aetiology of both colorectal cancer and non-insulin dependent diabetes mellitus, leading to the hypothesis that hyperinsulinaemia may promote colorectal cancer. We prospectively examined the association between colorectal cancer risk and factors related to insulin resistance and hyperinsulinaemia, including BMI, physical activity, diabetes mellitus, and blood glucose, in a cohort of 75 219 Norwegian men and women. Information on incident cases of colorectal cancer was made available from the Norwegian Cancer Registry. Reported P values are two-sided. During 12 years of follow up, 730 cases of colorectal cancer were registered. In men, but not in women, we found a negative association with leisure-time physical activity (P for trend = 0.002), with an age-adjusted RR for the highest versus the lowest category of activity of 0.54 (95% CI = 0.37-0.79). Women, but not men, with a history of diabetes were at increased risk of colorectal cancer (age-adjusted RR = 1.55; 95% CI = 1.04-2.31), as were women with non-fasting blood glucose > or = 8.0 mmol l(-1)(age-adjusted RR = 1.98; 95% CI = 1.31-2.98) compared with glucose <8.0 mmol l(-1). Overall, we found no association between BMI and risk of colorectal cancer. Additional adjustment including each of the main variables, marital status, and educational attainment did not materially change the results. We conclude that the inverse association between leisure-time physical activity and colorectal cancer in men, and the positive association between diabetes, blood glucose, and colorectal cancer in women, at least in part, support the hypothesis that insulin may act as a tumour promoter in colorectal carcinogenesis.     

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency questionnaires administered every 2 to 4 years starting in 1980. For the smoking analyses, 737 confirmed cases of epithelial ovarian cancer were identified and for the dietary aims, 507 cases were identified through June 1, 2004. RESULTS: Compared with never-smokers, neither current nor past smoking was associated with ovarian cancer risk overall; however, both were associated with mucinous tumors (n = 69; rate ratio [RR], past = 2.02 [95% confidence interval (CI), 1.15-3.55]; RR, current = 2.22 [95% CI, 1.16-4.24]). A modest inverse association between caffeine intake and ovarian cancer risk was observed (RR, top vs bottom quintile = 0.80; 95% CI, 0.60-1.07 [P = .03]), which was strongest for women who had never used either oral contraceptives (RR = 0.65; 95% CI, 0.46-0.92 [P for heterogeneity = .02]) or postmenopausal hormones (RR = 0.57; 95% CI, 0.36-0.91 [P for heterogeneity = .13]). Alcohol was not associated with ovarian cancer risk. CONCLUSIONS: The results of the current study suggest that cigarette smoking may only increase the risk for mucinous ovarian tumors, and alcohol intake was not associated with risk. However, an inverse association was observed between caffeine intake and ovarian cancer risk, particularly in women not using hormones; this finding merits further study.     

A prospective study of waist circumference and body mass index in relation to colorectal cancer incidence

OBJECTIVES: To study the association between waist circumference and colorectal cancer, and whether it is independent of body mass index (BMI). METHODS: Between 1997 and 2005, 953 incident colorectal cancer cases (546 men and 407 women) were identified among 95,151 participants (44,068 men and 51,083 women) from the Cancer Prevention Study-II Nutrition Cohort. RESULTS: Waist circumference was associated with increased colorectal cancer incidence in both men (multivariable adjusted rate ratio (RR) 1.68, 95% confidence interval (CI) 1.12-2.53 for waist circumference > or =120 cm compared to <95 cm, p trend = 0.006) and women (RR 1.75, 95% CI 1.20-2.54 for > or =110 compared to <85 cm, p trend = 0.003). High levels of BMI were also associated with increased risk. After adjustment for BMI, waist circumference remained associated with a nonstatistically significant increase in colorectal cancer incidence in both men (RR 1.41, 95% CI 0.81-2.45 for > or =120 compared to <95 cm, p trend = 0.10) and women (RR 1.48, 95% CI 0.89-2.48 for > or =110 compared to <85 cm, p trend = 0.13). CONCLUSIONS: Our results confirm that waist circumference is associated with increased colorectal cancer incidence, possibly partially independent of BMI.     

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.     

Calcium,vitamin D,dairy products,and risk of colorectal cancer in the Cancer Prevention Study II Nutrition Cohort (United States)

Objective: Calcium, vitamin D, and dairy product intake may reduce the risk of colorectal cancer. We therefore examined the association between these factors and risk of colorectal cancer in a large prospective cohort of United States men and women. Methods: Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed questionnaire on diet, medical history, and lifestyle in 1992–93. After excluding participants with a history of cancer or incomplete dietary information, 60,866 men and 66,883 women remained for analysis. During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women, respectively. Multivariate-adjusted rate ratios (RR) were calculated using Cox proportional hazards models. Results: Total calcium intake (from diet and supplements) was associated with marginally lower colorectal cancer risk in men and women (RR = 0.87, 95% CI 0.67–1.12, highest vs lowest quintiles, p trend = 0.02). The association was strongest for calcium from supplements (RR = 0.69, 95% CI 0.49–0.96 for 500 mg/day vs none). Total vitamin D intake (from diet and multivitamins) was also inversely associated with risk of colorectal cancer, particularly among men (RR = 0.71, 95% CI 0.51–0.98, p trend = 0.02). Dairy product intake was not related to overall risk. Conclusions: Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer. Vitamin D was associated with reduced risk of colorectal cancer only in men.     

Statin use and colorectal cancer risk according to molecular subtypes in two large prospective cohort studies

Use of statins is hypothesized to reduce colorectal cancer risk but the evidence remains inconsistent. This may be partly explained by differential associations according to tumor location or molecular subtypes of colorectal cancer. We examined the association between statin use and colorectal cancer risk according to tumor location, KRAS mutation status, microsatellite instability (MSI) status, PTGS2 (COX-2) expression, or CpG island methylator phenotype (CIMP) status in two large prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study. We applied Cox regression to a competing risks analysis. We identified 1,818 colorectal cancers during 1990 to 2006. Compared with nonusers, current statin use was not associated with colorectal cancer [relative risk (RR) = 0.99, 95% CI = 0.86-1.14] or colon cancer (RR = 1.10, 95% CI = 0.94-1.29) but was inversely associated with rectal cancer (RR = 0.59, 95% CI = 0.41-0.84, P(heterogeneity) < 0.001). When we examined the association within strata of KRAS mutation status, we found no association with KRAS-mutated cancers (RR = 1.20, 95% CI = 0.87-1.67) but did observe a possible inverse association among KRAS wild-type cancers (RR = 0.80, 95% CI = 0.60-1.06, P(heterogeneity) = 0.06). The association did not substantially differ by PTGS2 expression, MSI status, or CIMP status. Current statin use was not associated with risk of overall colorectal cancer. The possibility that statin use may be associated with lower risk of rectal cancer or KRAS wild-type colorectal cancer requires further confirmation.     

Cigarette smoking,use of other tobacco products and stomach cancer mortality in US adults: The Cancer Prevention Study II

Cigarette smoking is associated with increased risk of stomach cancer in many studies but there are limited data on this relationship in women and on risk associated with use of tobacco products other than cigarettes. We examined stomach cancer death rates in relation to cigarette smoking in women and use of cigarette, cigar, pipe, or smokeless tobacco in men in a nationwide prospective mortality study in the United States (US). Cohort follow-up from 1982-96 identified 996 and 509 stomach cancer deaths among 467,788 men and 588,053 women, respectively. Cox proportional hazards models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI) using non-users of tobacco as the referent group. Multivariate-adjusted RRs were the highest for men who currently smoked cigars (RR = 2.29, 95% CI = 1.49-3.51) or cigarettes (RR = 2.16, 95% CI = 1.75-2.67) and both increased with smoking duration. Women who currently (RR = 1.49, 95% CI = 1.18-1.88) or formerly (RR = 1.36, 95% CI = 1.08-1.71) smoked cigarettes were at significantly increased risk, as were men who formerly smoked cigarettes (RR = 1.55, 95% CI = 1.28-1.88), or currently (RR = 1.81, 95% CI = 1.40-2.35) or formerly (RR: 1.57, 95% CI = 1.22-2.03) used more than one type of tobacco. Men who reported a history of chronic indigestion or gastroduodenal ulcer had substantially higher mortality rates associated with current cigarette (RR = 3.45, 95% CI = 2.05-5.80) or cigar (RR = 8.93, 95% CI = 4.02-19.90) smoking, as did men who were current aspirin users. If causal, the estimated proportion of stomach cancer deaths attributable to tobacco use would be 28% in US men and 14% in women. We conclude that prolonged use of tobacco products is associated with increased stomach cancer mortality in men and women. The accumulated evidence from this and other studies support reconsidering stomach cancer as a tobacco-related cancer.     

Green tea and black tea consumption in relation to colorectal cancer risk: the Singapore Chinese Health Study

The relationships between green tea and black tea consumption and colorectal cancer risk were examined within the Singapore Chinese Health Study, a prospective cohort study of diet and cancer involving >60,000 men and women. Intake of green tea and black tea was assessed through in-person interviews. Incident cancer cases and deaths among cohort members were identified through record linkage of the cohort database with respective databases from the nationwide Singapore Cancer Registry and the Singapore Registry of Births and Deaths. The proportional hazard regression method was used to examine the associations between intake of green and black tea separately and colorectal cancer risk with adjustment for potential confounders. After an average of 8.9 years of follow-up, 845 colorectal cancer cases were identified. Subjects who drank green tea exhibited a statistically non-significant increase in risk [relative risk (RR) = 1.12, 95% confidence interval (CI) = 0.97-1.29] relative to non-drinkers of green tea. This risk increase was mainly confined to men (RR = 1.31, 95% CI = 1.08-1.58); the comparable RR in women was 0.89 (95% CI = 0.71-1.12). In men, the green tea-colorectal cancer association was noted mainly in those with advanced disease (Duke C or D) (RR = 1.53, 95% CI = 1.19-1.97), and the association was dose dependent (P for trend = 0.0002). This latter association was especially strong within the colon subsite (RR = 1.75, 95% CI = 1.24-2.46; P for trend < 0.0001). Irrespective of gender, intake of black tea was not associated with risk of colorectal cancer (RR = 0.92, 95% CI = 0.79-1.07) in this Asian population.     

Calcium intake and risk of colon cancer in women and men

BACKGROUND: Calcium has been hypothesized to reduce the risk of colon cancer, and in a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. We examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). METHODS: Our study population included 87 998 women in NHS and 47 344 men in HPFS who, at baseline (1980 for NHS and 1986 for HPFS), completed a food frequency questionnaire and provided information on medical history and lifestyle factors. Dietary information was updated at least every 4 years. During the follow-up period (1980 to May 31, 1996 for the NHS cohort; 1986 to January 31, 1996 for the HPFS cohort), 626 and 399 colon cancer cases were identified in women and men, respectively. Pooled logistic regression was used to estimate relative risks (RRs), and all statistical tests were two-sided. RESULTS: In women and men considered together, we found an inverse association between higher total calcium intake (>1250 mg/day versus < or =500 mg/day) and distal colon cancer (women: multivariate RR = 0.73, 95% confidence interval [CI] = 0.41 to 1.27; men: RR = 0.58, 95% CI = 0.32 to 1.05; pooled RR = 0.65, 95% CI = 0.43 to 0.98). No such association was found for proximal colon cancer (women: RR = 1.28, 95% CI = 0.75 to 2.16; men: RR = 0.92, 95% CI = 0.45 to 1.87; pooled RR = 1.14, 95% CI = 0.72 to 1.81). The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal. CONCLUSIONS: Higher calcium intake is associated with a reduced risk of distal colon cancer. The observed risk pattern was consistent with a threshold effect, suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction. Future investigations on this association should concentrate on specific cancer subsites and on the dose-response relationship.     

Associations between beer, wine, and liquor consumption and lung cancer risk: a meta-analysis.

OBJECTIVE: Epidemiologic studies suggest that the effect on lung cancer risk may be different for beer, wine, and liquor. We conducted dose-specific meta-analyses and dose-response meta-regression to summarize findings from the current literature on the association between consumption of beer, wine, or liquor and lung cancer risk. RESULTS: Average beer consumption of one drink or greater per day was associated with an increased risk of lung cancer [relative risk (RR), 1.23; 95% confidence interval (95% CI), 1.06-1.41]. This association was observed in both men and women, although it was only significant in men. A J-shaped dose-response curve was suggested for beer intake. An inverse association was observed for both average wine consumption of less than one drink per day (RR, 0.77; 95% CI, 0.59-1.00) and one drink or greater per day (RR, 0.78; 95% CI, 0.60-1.02) in the drinking range incurred in the source studies. Average liquor consumption of one drink or greater per day was found to be associated with increased risk in men (RR, 1.33; 95% CI, 1.10-1.62). No association was observed for liquor drinking in women. The presence of heterogeneity between studies was detected. Study design, country, gender, adjustment factors, and lung cancer histologic type were not significant predictors of the heterogeneity. CONCLUSIONS: The results from this meta-analysis suggest that high consumption of beer and liquors may be associated with increased lung cancer risk, whereas modest wine consumption may be inversely associated with risk. More research with improved control of confounding is needed to confirm these findings and to establish the dose-response relationship, particularly risk at high consumption levels.     

Dietary intakes of fruit,vegetables, and fiber,and risk of colorectal cancer in a prospective cohort of women (United States)

Objective: Although animal studies suggest an inverse association between consumption of plant foods and risk of colorectal cancer, many observational data have failed to support such an association. We prospectively examined the association between dietary intakes of fruit, vegetables, and fiber and colorectal cancer risk in a large female cohort from the Womens Health Study.Methods: Among 39,876 healthy women aged 45 years at baseline, 36,976 with baseline self-reported information on dietary intakes and other risk factors for colorectal cancer were included in the analyses. During an average follow-up of 10 years, 223 women were diagnosed with colorectal cancer. Intakes of fruit, vegetables, and fiber were assessed by a baseline food-frequency questionnaire. The analyses were carried out using the Cox proportional hazards regression and all tests were two-sided.Results: Intakes of fruit, vegetables, and the specific subgroups were not found to be associated with colorectal cancer risk. Multivariate relative risks (RRs) comparing the highest with lowest quintile were 0.79 (95% CI = 0.49–1.27,pfor trend = 0.30) for fruit intake, and 0.88 (95% CI=0.56–1.38,pfor trend=0.30) for vegetables intake. Similarly, intake of total fiber was not associated with colorectal cancer risk; the RR for the highest relative to lowest quintile was 0.75 (95% CI=0.48–1.17,pfor trend=0.12). However, higher intake of legume fiber was associated with a lower risk of colorectal cancer; the RR for the highestversuslowest quintile was 0.60 (95% CI=0.40–0.91,pfor trend=0.02).Conclusions: Our data offer little support for associations between intakes of fruit, vegetables, and fiber, and colorectal cancer risk. However, our data suggest that legume fiber and/or other related sources may reduce risk of colorectal cancer.     

Cigarette smoking and colorectal cancer mortality in the cancer prevention study II

BACKGROUND: Recent studies suggest that long-term cigarette smoking is associated with an increased risk of colorectal cancer. Whether the association is causal or due to confounding remains unclear. METHODS: We examined cigarette smoking in relation to colorectal cancer mortality, evaluating smoking duration and recency and controlling for potential confounders in the Cancer Prevention Study II. This prospective nationwide mortality study of 1 184 657 adults (age > or =30 years) was begun by the American Cancer Society in 1982. After exclusions, our analytic cohort included 312 332 men and 469 019 women, among whom 4432 colon or rectal cancer deaths occurred between 1982 and 1996 among individuals who were cancer free in 1982. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated by fitting Cox proportional hazards models. All statistical tests were two-sided. RESULTS: Multivariate-adjusted colorectal cancer mortality rates were highest among current smokers, were intermediate among former smokers, and were lowest in lifelong nonsmokers. The multivariate-adjusted RR (95% CI) for current compared with never smokers was 1.32 (1.16-1.49) among men and 1.41 (1.26-1.58) among women. Increased risk was evident after 20 or more years of smoking for men and women combined as compared with never smokers. Risk among current and former smokers increased with duration of smoking and average number of cigarettes smoked per day; risk in former smokers decreased significantly with years since quitting. If the multivariate-adjusted RR estimates in this study do, in fact, reflect causality, then approximately 12% of colorectal cancer deaths among both men and women in the general U.S. population in 1997 were attributable to smoking. CONCLUSIONS: Long-term cigarette smoking is associated with increased risk of colorectal cancer mortality in both men and women. Clear reduction in risk is observed with early smoking cessation.     

Dietary folate intake and k-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study

We studied the association between dietary folate and specific K-ras mutations in colon and rectal cancer in The Netherlands Cohort Study on diet and cancer. After 7.3 years of follow-up, 448 colon and 160 rectal cancer patients and 3,048 sub-cohort members (55-69 years at baseline) were available for data analyses. Mutation analysis of the K-ras gene was carried out on all archival adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer overall and for K-ras mutation status subgroups according to 100 mug/day increased intake in dietary folate. Dietary folate intake was not significantly associated with colon cancer risk for men or women, neither overall nor with K-ras mutation status. For rectal cancer, folate intake was associated with a decreased disease risk in men and was most pronounced for K-ras mutated tumors, whereas an increased association was observed for women. Regarding the K-ras mutation status in women, an increased association was observed for both wild-type and mutated K-ras tumors. Specifically, folate intake was associated with an increased risk of G>T and G>C transversions in rectal tumors (RR = 2.69, 95% CI = 1.43-5.09), but inversely associated with G>A transitions (RR = 0.08, 95% CI = 0.01-0.53). Our data suggest that the effect of folate on rectal cancer risk is different for men and women and depends on the K-ras mutation status of the tumor.