Breast cancer risk associated with gene expression and genotype polymorphisms of the folate-metabolizing MTHFR gene: a case-control study in a high altitude Ecuadorian mestizo population.
DFE was positively associated with breast cancer in MTHFR 677CT/TT-1298AA women (P for trend = 0.01) but inversely associated in compound heterozygous women (P for trend = 0.01).
This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk.
We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'-regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1).
The findings suggest that the MTHFRC677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.
SNPs in CYP1A1, CYP2A1, CYP2B6, CYP2C, CYP2D6, CYP3A, GSTM1, GSTT1, GSTP1, SULT1A1, SULT1A2, UGT, and MTHFR are associated with breast cancer susceptibility; however, lack of such associations are also reported in some populations.
Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-beta2 genes in breast cancer.
We found three single-nucleotide polymorphisms in those genes associated with LINE-1 methylation: SLC19A1 (rs1051266); MTRR (rs10380) and MTHFR (rs1537514), one of which was also associated with breast cancer risk: MTHFR (rs1537514).
PubMed, EBSCO, LILACS, Scopus, and Latin American-specific databases were searched for studies exploring the association between the MTHFR polymorphisms and breast cancer susceptibility in Latinos until January 2019.
Our data demonstrate for the first time a functional consequence of changes in intracellular folate cofactors resulting from the MTHFR 677T mutation in cells derived from the target organs of interest, thus providing a plausible cellular mechanism that may partly explain the site-specific modification of colon and breast cancer risks associated with the MTHFRC677T mutation.
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.
We evaluated MTHFR genotypes and breast cancer survival in a cohort of 1067 Chinese women diagnosed with breast cancer between 1996 and 1998 who received surgery and chemotherapy.
Our results indicate that MTHFRC677T T allele was associated with increased risk of breast cancer in Taiwan, especially in cases who were 45.4 old or younger and with earlier menarche age (<12.2 years).
Additionally, we summarized breast cancer risk associated with the following genetic factors: breast cancer susceptibility high-penetrance genes (BRCA1, BRCA2, p53, PTEN, ATM, NBS1 or LKB1) and low-penetrance genes such as cytochrome P450 genes (CYP1A1, CYP2D6, CYP19), glutathione S-transferase family (GSTM1, GSTP1), alcohol and one-carbon metabolism genes (ADH1C and MTHFR), DNA repair genes (XRCC1, XRCC3, ERCC4/XPF) and genes encoding cell signaling molecules (PR, ER, TNFalpha or HSP70).
The results of this study suggest that the MTHFR 677T variant genotype per se may have no overall association with breast cancer risk, but a sizable association could be observed in the presence of relevant environmental exposure.