Folate and one-carbon metabolism nutrients from supplements and diet in relation to breast cancer risk

Abstract

Background: Few epidemiologic studies have examined very high intakes of folate and whether consumption of nutrients involved in one-carbon metabolism is associated with breast cancer risk. Objective: We prospectively examined whether the consumption of folate and nutrients involved in one-carbon metabolism (methionine, riboflavin, and vitamins B-6 and B-12) from self-reported intakes of diet (in year before baseline) and supplements (averaged over 10 y before baseline) were associated with the incidence of breast cancer and breast cancer tumor characteristics. Design: Participants were 35,023 postmenopausal women aged 50-76 y in the VITamins And Lifestyle (VITAL) cohort study; breast cancer was diagnosed in 743 of these women between baseline (2000-2002) and 2006. Cox proportional hazards models were used to estimate multivariable-adjusted relative risks (RRs) and 95% CIs. Results: Women consuming !1272 dietary folate equivalents (DFE)/d of total folate (10-y average) had a 22% decrease in breast cancer risk compared with women consuming 345 DFE/d (RR: 0.78; 95% CI: 0.61, 0.99; P for trend ¼ 0.05). A greater benefit was observed for estrogen-receptor (ER) negative than for ER1 breast cancers (RR: 0.38; 95% CI: 0.18, 0.80; P for trend ¼ 0.02; P ¼ 0.02 for the difference between ER2 and ER1). Neither current intakes of folate nor current or long-term intakes of other one-carbon nutrients were significantly associated with breast cancer risk. Multivitamin use attenuated the increased risk of breast cancer associated with alcohol drinking (P for interaction ¼ 0.02). Conclusions: Our study of predominantly supplement users suggests that high intakes of folate averaged over 10 y do not increase breast cancer risk, but may be protective, particularly against ER2 breast cancers.

Association of dietary intake of folate and MTHFR genotype with breast cancer risk

“…Recently, several studies reported a protective effect of folate intake on breast cancer risk Yang et al, 2013;Islam et al, 2013). However, evidence from two recent studies have indicated an inverse association (Ericson et al, 2007;Maruti et al, 2009a), and some other studies have shown that the reduced risk only exists in certain populations, such as women with high levels of alcohol intake or premenopausal Chinese women (Levi et al, 2001;Shrubsole et al, 2011).…”

Interactions Between MTHFR C677T - A1298C Variants and Folic Acid Deficiency Affect Breast Cancer Risk in a Chinese Population

“…At least 30 different enzymes are involved in this complex pathway including methylenetetrahydrofolate reductase (MTHFR), methionine synthase, methionine synthase reductase, and thymidylate synthase (Kim et al, 1999;Suleeporn et al, 2010). Defects or polymorphic enzymes may alter the bioavailability of FA and influence cancer susceptibility (Maruti et al, 2009). MTHFR is responsible for the availability of methyl groups for biological methylation reactions and catalyzes the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is a co-substrate for homocysteine remethylation to methionine (Dhillon et al, 2009); mutations of MTHFR will alter the activity of the enzyme.…”

Choline and betaine intake and risk of breast cancer among post-menopausal women

“…Choline can convert to betaine, which can donate the methyl group to homocysteine as does folate, although the donation of the methyl group by betaine is limited to the liver and the kidney. Although two meta-analyses did not find an overall association between folate intake and breast cancer risk (Lewis et al, 2006;Larsson et al, 2007), in some studies, folate intake was inversely associated with breast cancer risk in the whole population (Ericson et al, 2007), or among alcohol drinkers (Zhang et al, 1999;Rohan et al, 2000), or with certain hormone receptor types of breast cancer (Zhang et al, 2005;Larsson et al, 2008;Maruti et al, 2008). Choline and betaine may reduce the risk of breast cancer in a manner similar to that of folate.…”