Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer

Department of Social and Preventive Medicine, College of Medicine, Hallym University, Chunchon, Korea.
Cancer Causes and Control (Impact Factor: 2.74). 11/2010; 21(11):1919-30. DOI: 10.1007/s10552-010-9620-8
Source: PubMed


Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies.
Study- and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model.
Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing ≥ 560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 μg/day increase in total folate intake.
These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer.

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    • "Thus folate or vitamin B 6 intake may have been lower in the present population than in North America, where folate fortification is mandatory and supplements are commonly used (Kim, 2008). While an earlier meta-analysis suggested that dietary folate intake, rather than total folate intake, was more strongly related to a decreased risk of colorectal cancer (Sanjoaquin et al., 2005), a recent pooled analysis of prospective studies in North America and Europe indicated that the decrease in colorectal cancer risk was greater for total folate intake than for dietary folate intake (Kim et al., 2010). As for vitamin B 6 , supplement use accounted for the majority of total intake and resulted in a wider range of the distribution of the intake in some study populations in North America (Larsson et al., 2010). "
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    ABSTRACT: One-carbon metabolism plays an important role in colorectal carcinogenesis. Meta-analyses have suggested protective associations of folate and vitamin B6 intakes with colorectal cancer primarily based on studies in Caucasians, and genetic polymorphisms pertaining to the folate metabolism have been a matter of interest. Less investigated are the roles of methionine synthase (MTR) and thymidylate synthetase (TS) polymorphisms in colorectal carcinogenesis. In a study of 816 cases and 815 community controls in Japan, we investigated associations of dietary intakes of folate, methionine, vitamin B2, vitamin B6, and vitamin B12 with colorectal cancer risk. The associations with MTR 2756A>G, MTRR 66A>G, and TSER repeat polymorphism were examined in 685 cases and 778 controls. Methionine and vitamin B12 intakes were inversely associated with colorectal cancer risk, but the associations were totally confounded by dietary calcium and n-3 fatty acids. The other nutrients showed no association with the risk even without adjustment for calcium and n-3 fatty acids. The TSER 2R allele was dose-dependently associated with an increased risk. The MTR and MTRR polymorphisms were unrelated to colorectal cancer risk. There was no measurable gene-gene or gene-nutrient interaction, but increased risk associated with the TSER 2R allele seemed to be confined to individuals with high folate status. This study does not support protective associations for folate and vitamin B6. The TSER 2R allele may confer an increased risk of colorectal cancer. The role of the TSER polymorphism in colorectal carcinogenesis may differ by ethnicity.
    Full-text · Article · Nov 2013 · Asian Pacific journal of cancer prevention: APJCP
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    • "Many epidemiological studies support the protective effect of folate in prevention of colorectal cancer. Most recently, a meta-analysis of 13 human studies shows a positive correlation between folate consumption and protection from colorectal cancer [69]. Accordingly, many rodent studies demonstrate that folate depletion increases tumorigenesis and/or the development of precursor lesions (aberrant crypt foci, ACF) in response to colon carcinogens. "
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    ABSTRACT: Fortification of grains has resulted in a positive public health outcome vis-a-vis reduced incidence of neural tube defects. Whether folate has a correspondingly beneficial effect on other disease outcomes is less clear. A role for dietary folate in the prevention of colorectal cancer has been established through epidemiological data. Experimental data aiming to further elucidate this relationship has been somewhat equivocal. Studies report that folate depletion increases DNA damage, mutagenesis, and chromosomal instability, all suggesting inhibited DNA repair. While these data connecting folate depletion and inhibition of DNA repair are convincing, we also present data demonstrating that genetic inhibition of DNA repair is protective in the development of preneoplastic colon lesions, both when folate is depleted and when it is not. The purpose of this paper is to (1) give an overview of the data demonstrating a DNA repair defect in response to folate depletion, and (2) critically compare and contrast the experimental designs utilized in folate/colorectal cancer research and the corresponding impact on tissue folate status and critical colorectal cancer endpoints. Our analysis suggests that there is still an important need for a comprehensive evaluation of the impact of differential dietary prescriptions on blood and tissue folate status.
    Full-text · Article · Oct 2012 · Journal of Oncology
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    • "between cruciferous vegetables intake and decreased risk of prostate cancer. As a common and major nutrient from daily vegetables, folate was believed to decrease risk of many cancer types, such as colon cancer, esophageal squamous cell carcinoma, esophageal adenocarcinoma and pancreatic cancer (Larsson et al., 2006; Kim et al., 2010), however, meta-analysis of six randomized controlled trials indicated association between a 24% increased risk of prostate cancer with folic acid intake (Wien et al., 2012). Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate-involved one carbon metabolism, which catalyzes the conversion of 5,10-methylenetetrahydrofolate (5,10-methylene-THF) to 5-methyltetrahydrofolate (5-methyl-THF). "
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    ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme involved in folate metabolism; a single nucleotide polymorphism (SNP) C677T has been reported to be linked with altered incidences of several diseases. We here conducted a meta-analysis of 15 published epidemiological studies with a total of 7306 cases and 8062 controls to evaluate its association with prostate cancer risk with overall and subgroup analyses. No statistical relationship was found overall with any genetic model (TT vs. CC: OR = 0.80, 95%CI = [0.62, 1.04], P = 0.094; CT vs. CC: OR = 0.97, 95%CI = [0.84; 1.12], P = 0.667; Dominant: OR = 0.94, 95%CI = [0.82; 1.07], P = 0.343; Recessive: OR = 0.81, 95%CI = [0.64; 1.04], P = 0.104), but after the exclusion of several studies, we could observe the homozygote TT to confer less susceptibility to prostate cancer in carriers; moreover, different effects of the polymorphism on prostate cancer risk was detected from subgroup analysis stratified by participants' residential region: significant reduced prostate cancer risk was found to be associated with the polymorphism from Asian studies (TT vs. CC: OR = 0.47, 95%CI = [0.33; 0.67], P< 0.001; CT vs. CC: OR = 0.73, 95%CI = [0.60; 0.90], P = 0.002; Dominant: OR = 0.67, 95%CI = [0.56; 0.82], P< 0.001; Recessive: OR = 0.55, 95%CI = [0.40; 0.76], P< 0.001) while studies from Europe indicated a slight increased risk under dominant model with marginal significance (OR = 1.14, 95%CI = [0.99; 1.30], P = 0.064). Moreover, the protective effect of the polymorphism against prostate cancer was also shown by studies performed in yellow Asians (TT vs. CC: OR = 0.48, 95%CI = [0.31; 0.75], P = 0.001; CT vs. CC: OR = 0.68, 95%CI = [0.51; 0.90], P = 0.006; Dominant: OR = 0.63, 95%CI = [0.48; 0.82], P < 0.001; Recessive: OR = 0.57, 95%CI = [0.39; 0.84], P = 0.004). We propose that these phenomena should be viewed with the consideration of folate metabolism profile and different gene background as well as living habits of different populations, and more relevant studies should be conducted to confirm our hypothesis and provide a comprehensive and clear picture concerning this topic.
    Preview · Article · Jun 2012 · Asian Pacific journal of cancer prevention: APJCP
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