Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women

Abstract

BackgroundSeveral studies have determined that dietary intake of B vitamins may be associated with breast cancer risk as a result of interactions between 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) in the one-carbon metabolism pathway. However, the association between B vitamin intake and breast cancer risk in Brazilian women in particular has not yet been investigated.MethodsA case-control study was conducted in São Paulo, Brazil, with 458 age-matched pairs of Brazilian women. Energy-adjusted intakes of folate, vitamin B6, and vitamin B12 were derived from a validated Food Frequency Questionnaire (FFQ). Genotyping was completed for MTHFR A1298C and C677T, and MTR A2756G polymorphisms. A logistical regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsNeither dietary intake of folate, vitamin B6, or vitamin B12 nor MTHFR polymorphisms were independently associated with breast cancer risk. Analysis stratified by menopausal status showed a significant association between placement in the highest tertile of folate intake and risk of breast cancer in premenopausal women (OR = 2.17, 95% CI: 1.23–3.83; Ptrend = 0.010). The MTR 2756GG genotype was associated with a higher risk of breast cancer than the 2756AA genotype (OR = 1.99, 95% CI = 1.01–3.92; Ptrend = 0.801), and statistically significant interactions with regard to risk were observed between the MTHFR A1298C polymorphism and folate (P = 0.024) or vitamin B6 (P = 0.043), and between the MTHFR C677T polymorphism and folate (P = 0.043) or vitamin B12 (P = 0.022).ConclusionMTHFR polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12 had no overall association with breast cancer risk. However, increased risk was observed in total women with the MTR 2756GG genotype and in premenopausal women with high folate intake. These findings, as well as significant interactions between MTHFR polymorphisms and B vitamins, warrant further investigation.

Single-nucleotide polymorphisms in one-carbon metabolism genes, Mediterranean diet and breast cancer risk: a case–control study in the Greek-Cypriot female population

“…Nonetheless, an increased BC risk, in subjects with a combination of a low dietary intake of one-carbon metabolism vitamins and the MTHFR 677TT alleles, was shown in a number of earlier studies in different populations, which is in agreement with our findings (Alshatwi 2010;Chen et al 2005;Gao et al 2009;Lee et al 2004;Maruti et al 2009;Shrubsole et al 2004). Interestingly, other studies evidenced a high BC risk in individuals with the variant MTHFR 677TT genotype and increased intake of folate (Ericson et al 2009;Ma et al 2009a;Stevens et al 2007). With respect to the MTHFR 1298A[C SNP, a study found that females with the MTHFR 1298AC and MTHFR 1298CC genotype and low dietary folate consumption, had an increased BC risk, results which are similar to our results (Ma et al 2009a).…”

“…In other studies, however, no statistically significant association between dietary intake and MTHFR polymorphisms in BC was found (Le Marchand et al 2004;Lissowska et al 2007;Liu et al 2013;Ma et al 2009b;Naushad et al 2011;Shrubsole et al 2006;Xu et al 2007). This discrepancy may be due to differences in several factors including ethnic background, small sample sizes, low allele frequencies or different dietary exposures (Chou et al 2006;Ma et al 2009a;Stevens et al 2007).…”

“…Interestingly, other studies evidenced a high BC risk in individuals with the variant MTHFR 677TT genotype and increased intake of folate (Ericson et al 2009;Ma et al 2009a;Stevens et al 2007). With respect to the MTHFR 1298A[C SNP, a study found that females with the MTHFR 1298AC and MTHFR 1298CC genotype and low dietary folate consumption, had an increased BC risk, results which are similar to our results (Ma et al 2009a). In other studies, however, no statistically significant association between dietary intake and MTHFR polymorphisms in BC was found (Le Marchand et al 2004;Lissowska et al 2007;Liu et al 2013;Ma et al 2009b;Naushad et al 2011;Shrubsole et al 2006;Xu et al 2007).…”

“…Nevertheless, it has been suggested that interactions between MTHFR, MTR SNPs and nutrients participating in the one-carbon metabolism could influence significantly the risk of BC, highlighting the biological importance of these associations (Xu and Chen 2009). However, results are still inconclusive (Lewis et al 2006;Ma et al 2009a). In addition, in the majority of the previous studies, only the effect of the intake of individual nutrients and not the effect of a combination of food groups as a dietary pattern was examined (Ericson et al 2009;Lissowska et al 2007;Maruti et al 2009).…”

“…At the same time, it catalyses the de-methylation of 5-methylTHF to tetrahydrofolate (THF), which is used for the synthesis of thymidylate (Shrubsole et al 2006). The MTR 2756A [G SNP (p.Asp919Gly, rs1805087) is the most common SNP in this gene (Ma et al 2009a). Although the effect of this MTR SNP on the activity of the enzyme is not yet fully defined, i.e.…”