Dietary folate and APC mutations in sporadic colorectal cancer

Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC(+)) and without (APC(-)) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC(-)colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P(trend) = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC(+) colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, P(trend) = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, P(trend) = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC(-) colon tumors, but folate intake was positively associated with APC(+) colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway.     

Relationship of folate,vitamin B-6, vitamin B-12, and methionine intake to incidence of colorectal cancers

It is hypothesized that diets deficient in folate, methionine, and vitamins B-6 and B-12 cause DNA hypomethylation and, as a result, increase risk of colorectal cancers. Furthermore, it is proposed that alcohol, a methyl group antagonist, increases risk of colorectal cancers among those with low intake of folate. Data from the Iowa Women's Health Study, a population-based cohort of incident cancer, were used to examine the relationship of folate, methionine, and vitamins B-6 and B-12 to occurrence of cancers of the colon (n = 598) and rectum (n = 123) over 13 yr of follow-up. There were no independent associations of folate, methionine, or vitamins B-6 and B-12 derived from a food frequency questionnaire with incidence of colon cancer. Adjusted relative risks (RRs) of rectal cancer were similar across categories of folate, vitamin B-12, and methionine intake, but RRs increased progressively with increasing intake of vitamin B-6 [P (for trend) = 0.03]. RRs suggested that incidence of cancer of the proximal colon was lower among those with 1) high folate and high vitamin B-12 intake [RR = 0.59, 95% confidence interval (CI) = 0.39-0.89] and 2) high folate and high vitamin B-6 intake (RR = 0.65, 95% CI = 0.50-0.84) than among those with the lowest intake of these nutrients. Incidence of cancer of the proximal colon was also somewhat lower among those with high folate and low alcohol intake (RR = 0.44, 95% CI = 0.22-0.89). Findings provide limited support for an association between dietary factors involved in DNA methylation and risk of cancers of the colon and rectum.     

The relations of alcoholic beverage use to colon and rectal cancer

The authors prospectively studied the incidence of cancers of the colon and rectum in 106,203 men and women, both white and black, who supplied data at northern California Kaiser Permanente facilities about use of alcoholic beverages in 1978-1984. Analysis controlling for age, sex, race, body mass index, coffee use, total serum cholesterol, and education showed a positive association of alcohol use to both types of cancer, which was stronger for rectal cancer (trend test, p = 0.03) than for colon cancer (trend test, p = 0.11). When persons with a daily intake of three or more drinks were compared with abstainers, relative risk for rectal cancer was 3.17 (95% confidence interval (CI): 1.05-9.57) and relative risk for colon cancer was 1.71 (95% CI: 0.92-3.19). Women with a daily intake of three or more drinks had a relative risk for colon cancer of 2.56 (95% CI: 1.03-6.40) compared with 1.16 (95% CI: 0.46-2.90) for men. Among drinkers, preference for wine, beer, or hard liquor had no significant independent relation to either type of cancer; those who preferred beer were at slightly greater risk of rectal cancer, but those who preferred wine were more likely to develop colon cancer. These data suggest that total alcohol use, but no one specific beverage type, is associated with increased risk of rectal cancer.     

Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark

OBJECTIVE: There is consistent evidence that alcohol increases the risk of breast cancer. It has been suggested that the increased risk associated with alcohol intake may be reduced by adequate intake of folate. Since many women consume alcohol, detection of a risk-reducing mechanism would have major public health implications. DESIGN: We therefore evaluated the possible interaction between alcohol and folate in a paired nested case-control study among postmenopausal women. SETTING: A total of 24 697 postmenopausal women were included in the 'Diet, Cancer and Health' follow-up study between December 1993 and May 1997. The cohort was followed until December 2000. The study included 388 cases of breast cancer and 388 randomly selected controls were used to estimate the breast cancer incidence rate ratio (IRR) in conditional logistic regression analysis. RESULTS: A previously established association between alcohol intake and risk of breast cancer was present mainly among women with low folate intake. An IRR of 1.19 (95% CI: 0.99-1.42) per 10 g average daily alcohol intake was found for women with a daily folate intake below 300 mug, while among women with a folate intake higher than 350 mug, we could not show an association between the alcohol intake and the breast cancer incidence rate (e.g. folate intake >400 mug; IRR of 1.01 (95% CI: 0.85-1.20)). CONCLUSION: The findings support the evidence that adequate folate intake may attenuate the risk of breast cancer associated with high alcohol intake. SPONSORSHIP: The Danish Cancer Society.     

Folate intake, alcohol use, and postmenopausal breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

BACKGROUND: Several epidemiologic studies suggest that higher folate intakes are associated with lower breast cancer risk, particularly in women with moderate alcohol consumption. OBJECTIVE: We investigated the association between dietary folate, alcohol consumption, and postmenopausal breast cancer in women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort. DESIGN: Dietary data were collected at study enrollment between 1993 and 2001. Folate content was assigned on the basis of prefortification (ie, pre-1998) databases. Of the 25 400 women participants with a baseline age of 55-74 y and with complete dietary and multivitamin information, 691 developed breast cancer between September 1993 and May 2003. We used Cox proportional hazard models with age as the underlying time metric to generate hazard ratios (HRs) and 95% CIs. RESULTS: The adjusted HRs were 1.19 (95% CI: 1.01, 1.41; P for trend = 0.04) for women reporting supplemental folic acid intake >/=400 mug/d compared with subjects reporting no supplemental intake. Comparison of the highest with the lowest quintile gave adjusted HRs of 1.04 (95% CI: 0.83, 1.31; P for trend = 0.56) and 1.32 (95% CI: 1.04, 1.68; P for trend = 0.03) for food and total folate intake, respectively. Alcohol consumption was positively associated with breast cancer risk (highest compared with lowest quintile: HR = 1.37; 95% CI: 1.08, 1.76; P for trend = 0.02); the risk was greatest in women with lower total folate intake. CONCLUSIONS: Our results do not support the hypothesis that high folate intake reduces breast cancer risk; instead, they suggest that a high intake, generally attributable to supplemental folic acid, may increase the risk in postmenopausal women. However, our results confirm previous studies showing positive associations between moderate alcohol consumption and breast cancer.     

Intake of folate and related nutrients in relation to risk of epithelial ovarian cancer

Assessments of the relation between folate intake and ovarian cancer risk have been limited and inconsistent. Therefore, the authors prospectively examined the association of dietary and supplemental intakes of folate, methionine, and vitamin B(6) with ovarian cancer risk among 80,254 Nurses' Health Study participants. Beginning in 1976, women completed biennial questionnaires assessing ovarian cancer risk factors; starting in 1980, food frequency questionnaires were administered every 2-4 years. During 22 years of follow-up (1980-2002), the authors confirmed 481 incident epithelial ovarian cancers. There were no associations between total folate (top quintile vs. bottom: relative risk (RR) = 1.21, 95% confidence interval (CI): 0.92, 1.60), methionine (RR = 1.00, 95% CI: 0.76, 1.33), dietary vitamin B(6) (RR = 1.09, 95% CI: 0.81, 1.47), or total vitamin B(6) (RR = 1.13, 95% CI: 0.85, 1.51) intake and ovarian cancer risk. Higher dietary folate was associated with a modestly decreased risk after exclusion of cases diagnosed during the 4 follow-up years after dietary assessment (RR = 0.66, 95% CI: 0.43, 1.03) and for the serous subtype (RR = 0.51, 95% CI: 0.31, 0.84). Results did not vary by alcohol intake, multivitamin use, menopausal status, or oral contraceptive use. There was little evidence that folate, methionine, and vitamin B(6) are important in ovarian cancer risk, although dietary folate was inversely associated with risk in some analyses.     

Education, socioeconomic status and risk of cancer of the colon and rectum.

BACKGROUND: Socioeconomic correlates of cancer of the large bowel differ in various countries and calendar periods and may differ for the colon and rectum. Thus, the relationship between education and social class and risk of cancers of the colon and rectum was considered. METHODS: Combination of two hospital-based case-control studies conducted in six Italian centres between 1985 and 1996. Cases were 3533 patients aged < 79, with histologically confirmed cancer of the colon (n = 2180) or rectum (n = 1353), and controls were 7062 patients admitted to hospital for a wide spectrum of acute, non-neoplastic, non-digestive tract diseases. RESULTS: Compared to individuals with < 7 years of education the multivariate odds ratios (OR) of colon cancer for those with > or = 16 years were 2.45 (95% confidence interval [CI]: 1.87-3.23) in men and 1.29 (95% CI: 0.88-1.90) in women, with significant trends in risk. No significant association emerged between education and risk of rectal cancer, with OR of 1.18 (95% CI: 0.83-1.70) and 1.01 (95% CI: 0.61-1.67) respectively for men and women in the highest educational category compared to the lowest. Social class was also related to colon cancer risk: the OR were 2.30 (95% CI: 1.82-2.90) in men and 1.33 (95% CI: 1.03-1.73) in women in the highest versus the lowest social class. No association was found between social class and rectal cancer risk, with OR of 1.18 for either men or women in the highest as compared to the lowest social class. No significant heterogeneity was found for the association between education and colon cancer risk in either sex across strata of age at diagnosis, coffee, alcohol and vegetable intake, family history of the disease, and in anatomical subsites within the colon. CONCLUSION: This study, based on a uniquely large dataset, indicates that there are different social class correlates for colon and rectal cancer. Consequently the two sites should not be combined in studies considering lifestyle factors in the aetiology of these neoplasms.     

Alcohol and the risk of colon and rectal cancer with mutations in the K-ras gene.

The first metabolite of alcohol, acetaldehyde, may trigger replication errors and mutations in DNA, which may predispose to developing colorectal cancer (CRC). In a prospective study on colon and rectal cancer, we investigated the following hypotheses: alcohol consumption is associated with an increased risk of mutations in the K-ras oncogene, and beer consumption is associated with an increased risk of G-->A mutations in this gene. Therefore, we studied the associations between consumption of alcohol and alcoholic beverages and the risk of CRC without and with specific K-ras gene mutations. In 1986, 120,852 men and women, aged 55-69 years, completed a questionnaire on risk factors for cancer. The case-cohort approach was used for data processing and analyses. After 7.3 years of follow-up, excluding the first 2.3 years, complete data from 4,076 subcohort members, 428 colon and 150 rectal cancer patients, were available for data analyses. Incidence rate ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. Compared to abstaining, a total alcohol consumption of 30.0 g/day and more was associated with the risk of colon and rectal cancer with and without a K-ras mutation in both men and women. Independent from alcohol intake, liquor consumption when compared to nonliquor consumption was associated with an increased risk of rectal cancer with a wild type K-ras in men (RR: 2.25, 95% CI: 1.0-5.0). Beer consumption was not clearly associated with the risk of colon and rectal tumors harboring G-->A mutations in the K-ras gene in men. This association could not be assessed in women because of sparse beer consumption. In conclusion, alcohol does not seem to be involved in predisposing to CRC through mutations in the K-ras gene, and specifically beer consumption is not associated with colon and rectal tumors harboring a G-->A mutation.     

Tea as a Potential Chemopreventive Agent in PhIP Carcinogenesis: Effects of Green Tea and Black Tea on PhIP-DNA Adduct Formation in Female F-344 Rats

Disturbances in DNA methylation have been hypothesized as being involved in carcinogenesis. It has been proposed that dietary factors such as folate, alcohol, and methionine may be associated with colon cancer because of their involvement in DNA methylation processes. Data from a large retrospective population‐based case‐control study of incident colon cancer were used to evaluate whether intake of alcohol and other dietary factors involved in DNA methylation are associated with colon cancer. Dietary data were obtained using a detailed diet history questionnaire. We did not observe strong independent associations between folate, vitamin B6, vitamin B12, methionine, or alcohol and risk of colon cancer after adjusting for body size, physical activity, cigarette smoking patterns, energy intake, and dietary intake of fiber and calcium. However, when assessing the associations between colon cancer and a composite dietary profile based on alcohol intake, methionine, folate, vitamin B12, and vitamin B6 we observed a trend of increasing risk as one moved from a low‐ to a high‐risk group. This trend was modest and most marked in those diagnosed at a younger age [odds ratio (OR) for men = 1.3, 95% confidence interval (CI) = 0.9–1.9; OR for women = 1.6, 95% CI= 1.0–2.6]. We observed that associations with this high‐risk dietary profile were greater among those who took aspirin or nonsteroidal anti‐inflammatory drugs on a regular basis and were younger at the time of diagnosis (men OR = 1.7, 95% CI = 1.0–3.2; women OR = 2.2, 95% CI= 1.0–4.8) and for distal tumors (men OR = 1.4, 95% CI = 0.9–2.3; women OR = 2.0, 95% CI = 1.0–3.8). Findings from this study provide only limited support for previously reported associations between dietary factors involved in DNA methylation and risk of colon cancer.     

Case-control analysis of dietary folate and risk of bladder cancer

Dietary folate, a water-soluble B vitamin found in a variety of fruits and vegetables, is of particular interest as a chemopreventive agent due to its role in DNA methylation and DNA synthesis and repair. We hypothesized that individuals with low folate intake would be at an increased risk for bladder cancer. Using an ongoing case-control study we assessed dietary folate in 409 incident bladder cancer patients and 451 healthy control subjects. A food-frequency questionnaire was used to estimate naturally occurring food folate (microg/kcal/day), dietary folate equivalents (DFE) from food sources (microg DFE/kcal/day), and DFE from all sources (microg DFE/kcal/day). Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Bladder cancer patients reported a statistically significant lower intake of folate than control subjects for food folate and DFE from food sources (P < 0.001) but not for DFE from all sources (P = 0.061). In the highest quartile of food folate intake there was a 54% reduced risk for bladder cancer (OR = 0.46; 95% CI = 0.29-0.73) after adjusting for age, gender, ethnicity, smoking, and total energy intake. Similarly, the highest quartile of intake was associated with a 59% reduced risk for DFE from food sources (OR = 0.41; 95% CI = 0.26-0.65) and a 35% reduced risk for DFE from all sources (OR = 0.65; 95% CI = 0.42-1.00). In the joint-effects analyses using never smokers with high folate intake as the reference group (OR = 1.0), heavy smokers with low food folate intake had a 2.31-fold (95% CI = 1.11-4.82) increased risk, whereas heavy smokers with high folate intake had a reduced OR of 1.31 (95% CI = 0.53-3.26). Although the ORs were not statistically significant, light smokers and high folate intake exhibited a protective effect (OR = 0.62; 95% CI = 0.20-1.94), whereas an increased risk was observed for light smoking and low folate intake (OR = 1.41; 95% CI = 0.57-3.45). These patterns were consistent for the joint effects of smoking and DFE from food sources and DFE from all sources. In summary, high intake of dietary folate was associated with an overall decrease in bladder cancer risk. These data may have important implications for cancer prevention; however, large, hypothesis-driven, population-based clinical trials will be required to confirm these findings.     

Colorectal Cancer Risk and Dietary Intake of Calcium,Vitamin D,and Dairy Products: A Meta-Analysis of 26,335 Cases From 60 Observational Studies

In vivo and in vitro studies suggest that dairy products, calcium, and dietary vitamin D inhibits the development of colorectal cancer (CRC). A meta-analysis was performed to evaluate this relationship in observational studies. Data from 60 epidemiological studies enrolling 26,335 CRC cases were pooled using a general variance-based meta-analytic method. Summary relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated for the highest vs. the lowest intake categories. Sensitivity analyses tested the robustness of these summary effect measures and the statistical heterogeneity. The summary RR for high milk and dairy product intake, respectively, on colon cancer risk was 0.78 (95% CI = 0.67–0.92) and 0.84 (95% CI = 0.75–0.95). Milk intake was unrelated to rectal cancer risk. High calcium intake had a greater protective effect against tumors of the distal colon and rectal cancer vs. proximal colon. The risk reduction associated with calcium was similar for dietary and supplemental sources. Vitamin D was associated with a nonsignificant 6% reduction in CRC risk. Higher consumption of milk/dairy products reduces the risk of colon cancer, and high calcium intake reduces the risk of CRC. Low vitamin D intake in the study populations may limit the ability to detect a protective effect if one exists.     

Energy balance and rectal cancer: an evaluation of energy intake, energy expenditure, and body mass index

Lack of energy balance, or greater energy intake than expenditure as indicated by a large body mass index (BMI), has been associated with colon cancer, although less is known about its association with rectal cancer. In this study, we examined the association between BMI, energy intake, and energy expenditure and their combined effect on rectal cancer risk. A population-based case-control study was conducted in Utah and Northern California. Incident cases (n = 952) of rectal cancer and population-based controls (n = 1205) were interviewed between 1997 and 2002 to obtain detailed information on body size, dietary intake, and physical activity patterns. BMI (kg/m(2)) was not associated with rectal cancer in either men or women. Participation in vigorous leisure-time physical activity over the past 20 yr was associated with a significant 40% reduction in rectal cancer risk. Energy intake was associated significantly with increased risk of rectal cancer, especially among people whose diagnosis was prior to age 60 yr (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.7-9.1 for men; OR = 2.8; 95% CI = 1.1-7.2 for women). There was a significant interaction between energy intake and energy expenditure, although not between BMI and either energy intake or energy expenditure. These data suggest that large BMI, an indicator of lack of energy balance, is not an important component of the etiology of rectal cancer. However, both physical activity and energy intake were significantly associated with rectal cancer risk. These data suggest that energy expenditure and energy intake alter rectal cancer risk through mechanisms other than energy balance.     

Energy Balance and Rectal Cancer: An Evaluation of Energy Intake,Energy Expenditure,and Body Mass Index

Lack of energy balance, or greater energy intake than expenditure as indicated by a large body mass index (BMI), has been associated with colon cancer, although less is known about its association with rectal cancer. In this study, we examined the association between BMI, energy intake, and energy expenditure and their combined effect on rectal cancer risk. A population-based case-control study was conducted in Utah and Northern California. Incident cases (n = 952) of rectal cancer and population-based controls (n = 1205) were interviewed between 1997 and 2002 to obtain detailed information on body size, dietary intake, and physical activity patterns. BMI (kg/m2) was not associated with rectal cancer in either men or women. Participation in vigorous leisure-time physical activity over the past 20 yr was associated with a significant 40% reduction in rectal cancer risk. Energy intake was associated significantly with increased risk of rectal cancer, especially among people whose diagnosis was prior to age 60 yr (odds ratio [OR] = 3.9; 95% confidence interval [CI] = 1.7-9.1 for men; OR = 2.8; 95% CI = 1.1-7.2 for women). There was a significant interaction between energy intake and energy expenditure, although not between BMI and either energy intake or energy expenditure. These data suggest that large BMI, an indicator of lack of energy balance, is not an important component of the etiology of rectal cancer. However, both physical activity and energy intake were significantly associated with rectal cancer risk. These data suggest that energy expenditure and energy intake alter rectal cancer risk through mechanisms other than energy balance.     

Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR_log2?=?1.06, 95% CI 0.99–1.14) or in men (HR_log2?=?0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR_log2?=?0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR_log2?=?1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women.     

Lifetime alcohol intake and risk of rectal cancer in western New York

The lifetime intake of total alcohol, beer, wine, and hard liquor was measured for 277 males and 145 females with pathologically confirmed, first, single, primary cancers of the rectum in western New York from 1978 to 1986. Controls who were age, sex, and neighborhood matched were also interviewed. Intake of beer and total alcohol was positively associated with rectal cancer risk. Most of the excess risk was found for the heaviest drinkers. Odds ratios for fourth quartile intakes for males were 1.80 (95% CI, 1.12, 2.89) for total alcohol and 1.86 (1.13, 3.06) for beer. No association was found with wine or hard liquor intake. Females drank considerably less in this population; trends were similar although not of as great magnitude as those for males. Adjustment for dietary risk factors did not change risk estimates appreciably. A high lifetime intake of beer and total alcohol was associated with an increased risk of rectal cancer, and this was independent of either socioeconomic status or diet.     

Lifetime alcohol intake and risk of rectal cancer in western New York

The lifetime intake of total alcohol, beer, wine, and hard liquor was measured for 277 males and 145 females with pathologically confirmed, first, single, primary cancers of the rectum in western New York from 1978 to 1986. Controls who were age, sex, and neighborhood matched were also interviewed. Intake of beer and total alcohol was positively associated with rectal cancer risk. Most of the excess risk was found for the heaviest drinkers. Odds ratios for fourth quartile intakes for males were 1.80 (95% CI, 1.12, 2.89) for total alcohol and 1.86 (1.13, 3.06) for beer. No association was found with wine or hard liquor intake. Females drank considerably less in this population; trends were similar although not of as great magnitude as those for males. Adjustment for dietary risk factors did not change risk estimates appreciably. A high lifetime intake of beer and total alcohol was associated with an increased risk of rectal cancer, and this was independent of either socioeconomic status or diet.     

Folate intake, serum homocysteine and methylenetetrahydrofolate reductase (MTHFR) C677T genotype are not associated with oral cancer risk in Puerto Rico

We examined the relationships between folate and methionine intake, serum homocysteine levels (as a biomarker for folate metabolism), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype and risk of oral cancer in a population-based, case-control study in Puerto Rico. Structured questionnaires were used to collect information on demographic factors, usual adult diet, and tobacco and alcohol use. Oral epithelial cells and blood samples were collected from a subset of subjects. Analyses were conducted by logistic regression, adjusting for age, sex, lifetime smoking and lifetime alcohol intake, with the following numbers of cases/controls, respectively: dietary data (341/521); MTHFR genotype (148/149); and homocysteine (60/90). Although increased folate intake was associated with decreased oral cancer risk [adjusted odds ratio (OR) in highest vs. lowest quartile = 0.6, 95% confidence interval (CI): 0.4, 1.0, P(trend) = 0.05)], this finding was due almost entirely to folate intake from fruit (adjusted OR = 0.4, 95% CI: 0.2, 0.6; P(trend) = 0.0001), whereas other dietary folate sources showed no clear association. Methionine intake and serum homocysteine levels were not associated with oral cancer risk. Subjects with the MTHFR C677T homozygous variant (TT) genotype had a nonsignificantly lower risk, and risk patterns tended to differ by level of folate, methionine, alcohol intake and smoking, although the power to detect significant associations in subgroups of these variables was low. Risks for oral cancer are not folate specific; preventive recommendations for this disease should emphasize the importance of a healthy diet, including substantial intake of fruits.     

Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.     

Association of fluids from beverages with risk of rectal cancer

Little information is available about how fluid intake from beverages and sources of fluid intake influence risk of rectal cancer. We examined these associations with risk of incident rectal cancer in a population-based case-control study of 952 cases and 1,205 controls living in northern California and Utah. We also determined if intake of fiber (soluble and insoluble), physical activity, and nonsteroidal anti-inflammatory medications (NSAIDs) or aspirin modified the associations between fluid intake and rectal cancer. We identified a modest inverse association of water intake (odds ratio, OR = 0.70; 95% confidence interval, CI = 0.48, 1.02) and total fluid intake (high vs. low OR = 0.70; 95% CI = 0.46, 1.06) with risk of rectal cancer in men and a positive association with juice among women (high vs. low OR = 1.56; 95% CI = 1.00, 2.41). Risk of rectal cancer increased nonsignificantly among men with beer consumption, among women with high white wine use, and among men and women with high long-term alcohol use. NSAIDs modified the association of alcohol consumption with rectal cancer: 1) risk associated with beer increased among men who did not take NSAIDs and had a high beer intake (OR = 1.60; 95% CI = 1.08, 2.39) and 2) risk associated with long-term alcohol intake increased in a linear fashion in women who did not use NSAIDs (OR = 1.98; 95% CI = 1.15, 3.40). Risk of rectal cancer increased among estrogen-negative women if they consumed any beer or white wine but decreased among estrogen-positive women with beer. In men, low intake of water and low insoluble fiber intake were associated with increased risk of rectal cancer beyond that of either factor alone (OR = 1.82; 95% CI = 1.11, 3.00). The interactions of fiber with water intake suggest that bowel motility may be the mechanism responsible for modification of rectal cancer risk for water. Associations of alcohol to risk for rectal cancer may be related to cellular hyperproliferation and may be modified by NSAID use.