Association of methylenetetrahydrofolate reductase and methionine synthase polymorphisms with breast cancer risk and interaction with folate, vitamin B6, and vitamin B12 intakes

Abstract

We assessed the association between dietary intake of folate and the MTHFR genotype with breast cancer in a Chinese population, with additional analysis of the interactions of gene polymorphisms and dietary intake of folate, vitamin B6, and vitamin B12. A case-control study was performed, and 535 patients with newly diagnosed breast cancer and 673 controls were enrolled into this study. The MTHFR 667TT genotype (odds ratio (OR) = 1.82, 95 % confidence interval (CI) = 1.24-2.97) and T allele (OR 0= 1.48, 95 % CI = 1.15-1.78) were correlated with a moderately significant increased risk of breast cancer when compared with the CC genotype. Individuals carrying the MTR 2756GG genotype (OR = 1.66, 95 % CI = 1.16-2.56) and G allele (OR = 1.42, 95 % CI = 1.26-1.81) had a higher risk of breast cancer when compared with subjects with the AA genotype. The MTHFR 667 T allele and MTR 2756 G allele were associated with a higher risk of breast cancer in individuals with low folate intake, vitamin B6, and vitamin B12, but the association disappeared among subjects with moderate and high intake of folate, vitamin B6, and vitamin B12. This case-control study found that the MTHFR C677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B6, and vitamin B12 intakes influence these associations.

Role of MTHFR C677T and MTR A2756G polymorphisms in thyroid and breast cancer development

“…Our results were similar to other studies addressing thyroid and breast cancers (Kotsopoulos et al, 2008;Kweon et al, 2014). For the MTR A2756G polymorphism, ours results have shown no association between this SNP and thyroid and breast cancers, which agreed with the results from 4 case-control breast cancer studies (Naushad et al, 2011;He et al, 2014;Jiang-hua et al, 2014;Weiwei et al, 2014). Meta-analyses by Zhong et al (2013) and Weiner et al (2012) also found no association between MTR A2756G polymorphism and breast cancer development.…”

“…Both studies included men and women. In a breast cancer case-control study conducted in Chinese women, an increased risk for cancer development was found in those carrying the 677TT genotype (He et al, 2014;Jiang-hua et al, 2014;Weiwei et al, 2014). These results were all in agreement with our present findings.…”

“…The MTHFR enzyme, encoded by the MTHFR gene, is responsible for catalyzing the irreversible reaction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, which is involved in DNA methylation, an important factor gene expression regulation. Alterations in DNA methylation due to polymorphisms in the MTHFR gene may be associated with cancer development (Yin et al, 2004;Alshatwi, 2010;Jiang-hua et al, 2014). The MTR enzyme is encoded by the MTR gene, and is responsible for catalyzing homocysteine remethylation to form methionine using the cofactor vitamin B 12.…”

“…The MTR enzyme is encoded by the MTR gene, and is responsible for catalyzing homocysteine remethylation to form methionine using the cofactor vitamin B 12. Polymorphisms in this gene increase homocysteine in the plasma, resulting in changes to the folate pathway, and can induce carcinogenesis (Weiner et al, 2012;Jiang-hua et al, 2014). According to several studies, MTHFR C677T and MTR A2756G polymorphisms are able to change folate metabolism, which is important for DNA synthesis and methylation, as well as genomic stability (Yin et al, 2004;Alshatwi, 2010;Weiner et al, 2012;Jiang-hua et al, 2014).…”

Population-level diversity in the association of genetic polymorphisms of one-carbon metabolism with breast cancer risk

“…TYMS 3′-UTR ins6/del6 showed positive association with breast cancer in the Japanese population (Zhai et al 2006), while it showed a null association in Indians (Naushad et al 2011), Chinese (Zhai et al 2006) and Germans (Justenhoven et al 2005). MTHFR C677T is the most widely studied polymorphism of this pathway; the segregation of data based on ethnic group or populations revealed a strong association of this polymorphism in Turkey (Deligezer et al 2005;Ozen et al 2013), China (Cheng et al 2008Gao et al 2009;Wu et al 2012;Jiang-Hua et al 2014), Syria (Lajin et al 2012), Morocco (Diakite et al 2012), and North America (Maruti et al 2009;Bentley et al 2010;Ramos-Silva et al 2015). Two studies, i.e., one on multi-ethnic group (Le Marchand et al 2004) and another on the Iranian population (Hosseini et al 2011), showed a protective role of this polymorphism.…”