Folate intake and risk of oral and pharyngeal cancer.

BACKGROUND: Diet has been recognised as having a role in the aetiology of oral and pharyngeal cancer, and dietary factors may account for 10-15% of cases in Europe. Folate deficiency has been linked to risk of several cancers, but has not been studied adequately with respect to oral cancer. PATIENTS AND METHODS: This case-control study, conducted in Italy and French-speaking Switzerland, included 749 patients with incident cancer of the oral cavity and pharynx, and 1772 hospital controls with acute, non-neoplastic conditions. The interviews used a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multiple logistic regression. RESULTS: The ORs were 0.68 (95% CI 0.52-0.88) for the intermediate tertile and 0.53 (95% CI 0.40-0.69) for the highest tertile of dietary folate intake, compared with the lowest tertile. No heterogeneity was found in strata of gender, age, methionine intake or alcohol consumption. The combined OR for low-folate and high-alcohol intake versus high-folate and low-alcohol intake was 22.3 (95% CI 13.1-38). CONCLUSIONS: Our study supports a protective role of folate against oral and pharyngeal carcinogenesis. Compared with low folate intake, a consistent reduction in risk was already observed from intermediate levels of intake, suggesting that cancer risk may be related to relative folate deficiency.     

Dietary folate intake and lung cancer risk in former smokers: a case-control analysis.

No studies have focused on the role of dietary folate intake in risk of lung cancer in former smokers, in whom dietary folate intake is less likely confounded with current smoking. Therefore, we evaluated the association between dietary folate intake and risk of lung cancer in a population of 470 histopathologically confirmed incident lung cancer cases from M. D. Anderson Cancer Center and 472 cancer-free controls from enrollees at a community-based multispecialty physician practice, frequency-matched on age (5 years), sex, and ethnicity. Dietary folate intake levels were estimated from a National Cancer Institute standard food frequency questionnaire. Unconditional logistic regression analyses were used to calculate the crude and adjusted ORs and their 95% CIs. Dietary folate intake from natural food was significantly higher among the controls than among the cases (P < 0.001), and folate intake above the control median value was associated with a 40% decreased risk of lung cancer (adjusted OR, 0.60; 95% CI, 0.45-0.79). A significant inverse dose-response relationship between increasing dietary folate and decreasing risk of lung cancer was also evident (adjusted OR, 1.02; 95% CI, 0.71-1.47; OR, 0.67; 95% CI, 0.46-0.99; and OR, 0.53; 95% CI, 0.35-0.80 for the second, third, and fourth quartiles of average folate intake, respectively; P for trend <0.001). A more pronounced inverse association between dietary folate intake and lung cancer risk was observed among subjects who drank alcohol, had smoked relatively more, those who did not take supplemental folate, and those who reported a family history of lung cancer. Our data suggest that there is a possible protective role of dietary folate in lung carcinogenesis, a finding which may have implications in public health and cancer prevention.     

Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study

Folate is involved in DNA synthesis, repair, and methylation. It has been hypothesized that high intake of folate may reduce the risk of human cancers, including cancer of the breast. Using data from a population-based case-control study of breast cancer conducted in urban Shanghai during 1996-1998, we evaluated the association of dietary folate intake and breast cancer risk among 1321 cases and 1382 controls, 25-64 years of age, who never drank alcohol regularly or used vitamin supplements. Usual dietary habits were assessed with an in-person, interviewer-administered food frequency questionnaire developed and tested for use in this population. Unconditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (95% CIs) after adjusting for potential confounding factors. Dietary folate intake was inversely associated with breast cancer risk (P for trend, 0.05) with an adjusted OR of 0.71 (95% CI, 0.56-0.92) observed among women who were in the highest quintile of intake. The inverse association was stronger after further adjusting for total fruit and vegetable and animal food intakes (OR, 0.62; 95% CI, 0.46-0.82; P for trend, 0.01). A more pronounced inverse association between folate intake and breast cancer risk (OR, 0.47; 95% CI, 0.25-0.88; P for trend, 0.01) was observed among women who consumed high levels of folate cofactors (methionine, vitamin B(12), and vitamin B(6)) than those whose intake levels of these nutrients were low. Dietary intake of methionine, vitamin B(12), and vitamin B(6) were not independently related to risk of breast cancer after adjusting for confounding factors. Thus, our study adds additional support to the protective role of dietary folate in breast carcinogenesis and suggests further that the effect of folate may be modified by dietary intake of methionine, vitamin B(12), and vitamin B(6).     

Dietary folate intake and the risk of 11 types of cancer: a case–control study in Uruguay

BackgroundThere is limited, but inconclusive, epidemiological evidence that high folate intake decreases the risk of colorectal and esophageal cancers. For other cancer sites, the evidence is even less consistent or extensive.Materials and methodsWe conducted a case–control study of dietary folate intake and risk of 11 cancer sites in Uruguay between 1996 and 2004, including 3539 cancer cases and 2032 hospital controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of cancer associated with folate intake.ResultsIn the multivariable model, there was a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.49, 95% CI 0.24–0.98), esophagus (OR = 0.29, 95% CI 0.14–0.60), upper aerodigestive tract (OR = 0.41, 95% CI 0.26–0.65), colorectum (OR = 0.42, 95% CI 0.23–0.76) and kidney (OR = 0.35, 95% CI 0.13–0.93) for the highest versus the lowest quartile of dietary folate intake.ConclusionsOur results not only confirm earlier findings of decreased risk of colorectal and esophageal cancers with a high dietary folate intake but also suggest decreased risk of several other cancers. However, we cannot exclude the possibility that residual confounding, multiple comparisons or other forms of bias could explain these results.     

Folate-related genes and the risk of tobacco-related cancers in Central Europe

Folate has been hypothesized to protect against aero-digestive cancers although the evidence is not yet conclusive due to possible confounding by other dietary factors. Sequence variants in folate pathway were suggested to be associated with plasma folate levels and are unlikely to be confounded by other lifestyle factors. We therefore investigated the effects of key folate genetic variants on the risk of aero-digestive cancers and their potential effect modification by folate intake in a multicenter study in Central Europe. A total of 2250 lung cases, 811 upper aero-digestive tract cases and 2899 controls were recruited with blood samples. The methylenetetrahydrofolate reductase (MTHFR) C677T variant was associated with an increased risk of lung cancer with an odds ratio (OR) for homozygote variant of 1.37 [95% confidence interval (CI) = 1.10-1.71]. The two MTHFR variants were in strong linkage disequilibrium, and 677T-1298A appeared to be the primary haplotype associated with cancer risk. The risk estimates for MTHFR 677T/677T genotype was more prominent among lung cancer patients with young onset (OR = 1.92, 95% CI = 1.12-3.29). When stratified by dietary intake of folate, the effect of the MTHFR 677T variant was more prominent among subjects with low intake of folate: the ORs for 677T/677T genotype among subjects with the lowest decile were 2.60 (95% CI = 1.39-4.88) and 4.14 (95% CI = 1.47-11.7) for lung and upper aero-digestive tract cancer, respectively. In conclusion, we identified a moderate effect of MTHFR C677T on lung cancer risk and a possible effect modification by folate intake that is consistent with the functional data. These results support an important role of folate in protecting against tobacco-related cancers.     

Macronutrients, fatty acids, cholesterol and prostate cancer risk.

BACKGROUND: The role of selected macronutrients, fatty acids and cholesterol in the etiology of prostate cancer was analyzed using data from a case-control study carried out in five Italian areas between 1991 and 2002. PATIENTS AND METHODS: Cases were 1294 men with incident, histologically confirmed prostate cancer, and admitted to the major teaching and general hospitals of study areas. Controls were 1451 men admitted for acute, non-neoplastic conditions to the same hospital network. Information on dietary habits was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for increasing levels of nutrient intake. RESULTS: A direct association with prostate cancer was found for starch intake (OR = 1.4 in the highest versus the lowest quintile of intake; 95% CI: 1.1-1.8), whereas an inverse association emerged for polyunsaturated fatty acids (OR = 0.8; 95% CI: 0.6-1.0). Among polyunsaturated fatty acids, linolenic acid (OR = 0.7; 95% CI: 0.6-0.9) and linoleic acid (OR = 0.8; 95% CI: 0.6-1.0) were inversely related to prostate cancer. When the six major macronutrients were included in the same model, the adverse effect of high intake of starch and monounsaturated fatty acids was statistically significant together with the protective effect of polyunsaturated fatty acids. Results were consistent in separate strata of age, body mass index and family history of prostate cancer. CONCLUSIONS: Starch and monounsaturated fatty acids were directly associated with prostate cancer risk and polyunsaturated fatty acids were inversely associated.     

One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer

Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% CI), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.     

Green tea intake, MTHFR/TYMS genotype and breast cancer risk: the Singapore Chinese Health Study

The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been reported to act as a cancer preventive agent through folate pathway inhibition in experimental studies. We hypothesized that if folate pathway inhibition is the mechanism of cancer preventive activities of EGCG, then the protective effect against breast cancer would be stronger among women with low dietary folate intake and the high-activity methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genotypes. In a nested case-control study of 380 women with incident breast cancer and 662 controls within the Singapore Chinese Health Study, we found no association between either green tea intake or gene polymorphisms of MTHFR (C677T and A1298C) and TYMS (1494 ins/del) and breast cancer risk. However, among women with low folate intake (<133.4 microg/day), weekly/daily green tea intake was inversely associated with breast cancer risk compared with less green tea intake [odds ratio (OR) = 0.45, 95% confidence interval (CI) = 0.26-0.79, P for interaction = 0.02]. Among women with high folate intake (>or=133.4 microg/day), green tea intake was not associated with breast cancer. Similarly, among women possessing the high-activity MTHFR/TYMS genotypes (0-1 variant allele), weekly/daily versus less frequent green tea intake was associated with lower breast cancer risk (OR = 0.66, 95% CI = 0.45-0.98), which was observed even more strongly among those who also had low folate intake (OR = 0.44, 95% CI = 0.22-0.89) than high folate intake (OR = 0.92, 95% CI = 0.55-1.54). This association was not observed among women possessing the low-activity genotypes (2-4 variant alleles). Our findings suggest that folate pathway inhibition may be one mechanism through which green tea protects against breast cancer in humans.     

Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene.

We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis.     

Diets, polymorphisms of methylenetetrahydrofolate reductase, and the susceptibility of colon cancer and rectal cancer

The aim of this study was to investigate the association of environmental factors (dietary folate, methionine and drinking status) and polymorphisms in the methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) gene, as well as the combination of these factors, with the risk of colon cancer and rectal cancer. A case-control study of 53 colon cancer patients, 73 rectal cancer patients and 343 healthy controls was conducted. Genotypes of C677T and A1298C polymorphisms were analyzed by PCR-RFLP. The dietary folate and methionine intakes were assessed using food-frequency questionnaires and food consumption tables. Unconditional logistic regression was applied to estimate the odds ratios (ORs) and their 95% confidence intervals (CIs). The frequency of MTHFR 677T and 1298C alleles in healthy population were 39.4 and 17.2%, respectively. After adjustment for specific variants, the MTHFR 677TT genotype showed a significantly reduced risk of colon cancer compared with the wild type (OR=0.22, 95% CI: 0.50-0.98), and 1298C allele-carrier showed an inverse association with the risk of rectal cancer compared to the wild type (OR=0.52, 95% CI: 0.28-0.98). Adequate intake of folate was a protective factor from colon cancer (OR=0.32, 95% CI: 0.12-0.88) and MTHFR C677T polymorphism showed a statistically significant effect (OR=0.25, 95% CI: 0.06-0.93), reducing the risk of colon cancer in groups that have an intake of folate exceeding 115.64ng per 1000kcal per day. This study suggests that MTHFR C677T and A1298C polymorphisms are associated with the reduced risk of colon and rectal cancers, respectively. Adequate folate intake shows an inverse association with the risk of colon cancer. There is a significant interaction between MTHFR C677T polymorphism and folate intake in reducing the risk of colon cancer.     

Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study.

The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospective Health Professionals Follow-up Study. We matched 450 incident prostate cancer cases diagnosed from 1993-1998 to 450 controls by age, time, month, and year of blood donation. Modest inverse, but not statistically significant, associations were observed among plasma alpha-carotene, beta-carotene, and lycopene concentrations, and overall risk of prostate cancer diagnosis [odds ratio (highest versus lowest quintile; OR), alpha-carotene: OR, 0.67 [95% confidence interval (CI), -0.40-1.09]; beta-carotene: OR, 0.78 (95% CI, 0.48-1.25); lycopene: OR, 0.66 (95% CI, 0.38-1.13)]. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older (OR, 0.47; 95% CI, 0.23-0.98) and without a family history of prostate cancer (OR, 0.48; 95% CI, 0.26-0.89). Combining, older age and a negative family history provided similar results (OR, 0.43; 95% CI, 0.18-1.02). Inverse associations between beta-carotene and prostate cancer risk were also found among younger participants (<65 years of age; OR, 0.36; 95% CI, 0.14-0.91; P(trend) = 0.03). Combining dietary intake and plasma data confirmed our results. We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer, which was restricted to older participants and those without a family history of prostate cancer. This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component. In addition, our findings also suggest that among younger men, diets rich in beta-carotene may also play a protective role in prostate carcinogenesis.     

Functional variant of manganese superoxide dismutase (SOD2 V16A) polymorphism is associated with prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer study.

Superoxide dismutase (SOD) plays a key role in the detoxification of superoxide free radicals. We evaluated the association of prostate cancer with genetic polymorphisms in SOD1 (CuZn-SOD; IVS3-251A>G), SOD2 [MnSOD; Ex2+24T>C (V16A)], and SOD3 (EC-SOD; IVS1+186C>T, Ex3-631C>G, Ex3-516C>T, and Ex3-489C>T), the three main isoforms of SOD. Prostate cancer cases (n = 1,320) from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial were frequency matched to nondiseased controls (n = 1,842) by age, race, time since initial screening, and year of blood draw. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI); stratified analysis by the level of antioxidative vitamins was also conducted. The higher activity Ala variant at SOD2 Ex2+24T>C (V16A), which has been hypothesized to suppress prostate carcinogenesis, was associated with elevation of prostate cancer risk in Caucasians (Val/Ala versus Val/Val: OR, 1.17; 95% CI, 0.97-1.42; Ala/Ala versus Val/Val: OR, 1.28; 95% CI, 1.03-1.60; P(trend) = 0.03). Stratification by quartiles of dietary and supplemental vitamin E intake (IU/d) showed risks of prostate cancer tended to be increased among SOD2 Ala allele carriers, except at the highest quartile of vitamin E intake (>222; P(interaction) = 0.06, Q1-Q3 versus Q4). The association between Ala allele and prostate cancer risk among those with lower intake of vitamin E (相似文献   

Dietary folate intake, MTHFR genetic polymorphisms, and the risk of endometrial cancer among Chinese women.

Folate plays an important role in carcinogenesis. The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), encoded by the MTHFR gene, is involved in this process. We investigated both the independent and joint effects of dietary folate and other methyl-related nutrients, as well as three polymorphisms of MTHFR (677C>T, 1298A>C, and 1793G>A), on endometrial cancer risk in a population-based case-control study. Between 1997 and 2003, 1,204 newly diagnosed endometrial cancer cases and 1,212 controls were recruited among women between the ages of 30 and 69 years in urban Shanghai, China. Information on dietary intake of folate and other methyl-related nutrients, including vitamin B2 (riboflavin), vitamin B6, vitamin B12, and methionine, was derived from a validated food frequency questionnaire. Genotyping was completed on 1,041 cases and 1,030 controls for MTHFR 677C>T (rs1801133), 1298A>C (rs1801131), and 1793 G>A (rs2274967) [corrected] Haplotype estimation of the three single-nucleotide polymorphisms was performed using PHASE software. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate associations of nutrients, MTHFR genotypes, and haplotypes with endometrial cancer risk. A significant inverse association between dietary folate intake and endometrial cancer risk was observed among all subjects and non-B vitamin supplement users. The greatest reduction in endometrial cancer risk was observed among non-users of supplements in the highest quartile of dietary folate intake (OR, 0.5; 95% CI, 0.4-0.7) as compared with those in the lowest quartile. Dietary intake of folate cofactors (methionine, vitamin B2, vitamin B6, and vitamin B12) was not related to risk of endometrial cancer. No association was observed between endometrial cancer and the MTHFR 677C>T, 1298 A>C, and 1793G>A polymorphisms or derived haplotypes. Among non-users of supplements, however, the 1298C and 1793A alleles were associated with a lower risk of endometrial cancer among women with high dietary folate intake but related to a higher risk among those with low dietary folate intake (P(interaction) = 0.08 and 0.03, respectively). Further analysis showed that the lowest risk (OR, 0.6; 95% CI, 0.4-1.1) was among women with the 1298C allele and the highest intake of both folate and riboflavin (P(interaction) = 0.04). A similar association was observed for the 1793A allele (P(interaction) = 0.03). Our findings suggest that folate intake may decrease the risk of endometrial cancer and modify the effect of MTHFR polymorphisms on risk.     

Iron intake, oxidative stress-related genes (MnSOD and MPO) and prostate cancer risk in CARET cohort

Iron overload may increase prostate cancer risk through stimulation of oxidative stress, and endogenous pro- and antioxidant capabilities, i.e. manganese superoxide dismutase (MnSOD) and myeloperoxidase (MPO), may modify these associations. We investigated this hypothesis in the Carotene and Retinol Efficacy Trial cohort in a nested case-control study. Although there was no association between iron intake and risk overall, there was a suggestion of increased risk of clinically aggressive prostate cancer with higher iron intake [odds ratio (OR) = 1.4, 95% confidence interval (CI) = 0.9-2.0]. Associations were most notable for men with aggressive prostate cancer who were below the median consumption of total fruits and vegetables (OR = 1.8, 95% CI = 1.1-3.2). Associations between MPO -463 G to A genotype (rs2333227) and prostate cancer risk were only noted among men with aggressive cancer, with more than a 2-fold risk reduction among men with AA genotypes (OR = 0.4, 95% CI = 0.2-1.0); MnSOD was not associated with risk overall, but the MnSOD T to C (Val-9Ala, rs4880) polymorphism modified associations between risk of clinically aggressive prostate cancer and dietary iron intake (P for interaction = 0.02). Among aggressive cancer cases with the TT genotype, higher iron intake level was associated with >2-fold increase in risk (OR = 2.3, 95% CI = 1.0-4.9), whereas there was no association among men with CC genotypes (OR = 0.9, 95% CI = 0.4-2.3). Although interactions were not significant, there were similar patterns for MPO genotype, iron intake and risk. These findings suggest that higher iron intake may be associated with risk of clinically aggressive prostate cancer, and that endogenous antioxidant capabilities may modify these associations.     

Folate intake and the risk of breast cancer: a systematic review and meta-analysis

There is conflicting epidemiological evidence on the role of folate and breast cancer risk. We conducted a systematic review and quantitative meta-analysis of folate intake and folate blood levels and the risk of breast cancer. Four electronic databases (Medline, PubMed, Embase, and Current Contents Connect) were searched to April 11, 2014, with no language restrictions for observational studies that measured folate intake or blood levels and the risk of breast cancer. The meta-analysis of dietary folate intake comprising 36 studies with 34,602 cases, and a total sample size of 608,265 showed a decreased risk of breast cancer, with an odds ratio (OR) of 0.84 [95 % confidence interval (CI) 0.77–0.91]. When stratified by menopausal status and by study design, none of the meta-analyses of prospective studies showed any statistically significant decrease in the risk of breast cancer. The meta-analysis of total folate showed no statistically significant association with breast cancer OR of 0.98 (95 % CI 0.91–1.07). There was no significant association between either dietary or total folate intake and breast cancer when stratified by hormonal receptor status. The meta-analysis of blood folate levels found no significant association with the risk of breast cancer, with an OR of 0.86 (95 % CI 0.60–1.25). Breast cancer does not appear to be associated with folate intake, and this did not vary by menopausal status or hormonal receptor status. Folate blood levels also do not appear to be associated with breast cancer risk.     

Methylenetetrahydrofolate reductase, diet, and risk of colon cancer.

Individuals with different forms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, carriers of the C677T mutation versus wild type, show differences in enzyme levels; these differences have been hypothesized to be related to DNA methylation and, perhaps, to the nucleotide pool size. Using data from an incident case-control study, we evaluated the combined effect of dietary intake of folate, methionine, vitamin B6, vitamin B12, and alcohol and various forms of the MTHFR gene on risk of colon cancer. Individuals homozygous for the variant form of the MTHFR gene (TT) had a slightly lower risk of colon cancer than did individuals who were wild type [CC, odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6-1.1 for men; and OR = 0.9, 95% CI = 0.6-1.2 for women]. High levels of intake of folate, vitamin B6, and vitamin B12 were associated with a 30-40% reduction in risk of colon cancer among those with the TT relative to those with low levels of intake who were CC genotype. Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a halving of risk among those with the TT genotype. The inverse association with high levels of these nutrients in those with the TT genotype was stronger among those diagnosed at an older age. Although imprecise, the inverse association with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0.1-0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4-1.0), but this association was not seen with the high-risk diet for either the TT or CC/CT genotype. Although associations were generally weak, these findings suggest that those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B6, and vitamin B12.     

5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites.

We evaluated polymorphisms in methylenetetrahydrofolate reductase (MTHFR), folate intake and alcohol consumption in relation to risk of colon cancer in a population-based case-control study in North Carolina. The study included 555 cases (244 African Americans and 311 whites) and 875 controls (331 African Americans and 544 whites). Total folate intake of <400 versus > or =400 microg/day showed a weak positive association with colon cancer among both African Americans [adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.0-2.0] and whites (OR = 1.6, 95% CI = 1.2-2.2). No association was observed with use of alcohol. Compared with wild-type genotypes, there was no association between the low activity MTHFR codon 677 TT genotype and colon cancer, but the low activity codon 1298 CC genotype was inversely associated with colon cancer in whites (OR = 0.5, 95% CI = 0.3-0.9). Unlike previous studies, we did not observe a strong protective effect of the codon 677 TT low-activity genotype when folate intake was high. Instead, we observed an increased risk of colon cancer when folate intake was low for participants with wild- type genotypes. Adjusted ORs for the combined effects of codon 677 CC and codon 1298 AA genotypes and folate intake <400 microg/day were 1.9 (95% CI = 1.1-3.4) in African Americans and 2.5 (95% CI = 1.2-5.2) in whites. Our results suggest that variation at MTHFR codon 1298 (within the COOH-terminal region) may be more important for colon cancer than variation at codon 677 (NH(2)-terminal region), and in populations where folate intake is low, wild-type MTHFR activity may increase risk for colon cancer.     

Meat Consumption,Related Nutrients,Obesity and Risk of Prostate Cancer: a Case-Control Study in Uruguay

Background: In order to determine the role of meat consumption and related nutrients in the etiology of prostate cancer we conducted a case-control study among Uruguayan men in the time period 1998-2007. Results: The study included 464 cases and 472 controls, frequency matched for age and residence. Both series were drawn from the four major public hospitals in Montevideo. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (95 % CI) of prostate cancer by quartiles of meat intake and related nutrients. The highest vs. the lowest quartile of intake of total meat (OR = 5.19, 95 % CI 3.46-7.81), red meat (OR = 4.64, 95 % CI 3.10-6.95), and processed meat (OR = 1.78, 95% CI 1.22-2.59) were associated with increased risk of prostate cancer. Meat nutrients were directly associated with the risk of prostate cancer (OR for cholesterol 5.61, 95 % CI 3.75-8.50). Moreover, both total meat and red meat displayed higher risks among obese patients. Conclusions: This study suggests that total and red meat and meat nutrients may play a role in the etiology of prostate cancer in Uruguay.     

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and risk of gastric cancer in a Chinese population: a case-control study

Low dietary folate intake has been associated with increased risk of gastric cancer. The 5,10-methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has 2 variants, C677T and A1298C, that result in decreased MTHFR activity and lower plasma folate levels. Therefore, we hypothesized that these 2 variants play a role in gastric carcinogenesis. We tested this hypothesis in a Chinese population-based case-control study of 187 histopathologically confirmed gastric cancer cases and 166 healthy controls frequency-matched by age (+/-5 years), gender and residential area. The 677TT genotype was associated with increased risk for gastric cancer [adjusted odds ratio (OR) = 1.87, 95% confidence interval (CI) = 1.00-3.48] compared to the 677CC genotype. This association was more pronounced for gastric cardia cancer (adjusted OR = 2.47, 95% CI = 1.14-5.32). However, no evidence was found for risk associated with the MTHFR A1298C polymorphism. Our findings support the hypothesis that MTHFR C677T variants contribute to gastric carcinogenesis, particularly in gastric cardia. Larger studies incorporating dietary folate intake and serum levels are needed to confirm our findings.     

Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.