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.
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).
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).
There was also a significant interaction between FGFR2 rs2981582 and MTHFRrs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively).
This case-control study found that the MTHFRC677T and MTR A2756G polymorphisms are associated with risk of breast cancer, and folate, vitamin B6, and vitamin B12 intakes influence these associations.
In summary, during this meta-analysis, we found that MTHFRC677T polymorphism was significantly associated with breast cancer risk in the Chinese population.
Our study indicated that the MTHFRC665T polymorphism and vitamin B6 are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer.
Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group.
A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results.
The aim of the present study was to search for an association of the protease activated receptor (PAR)1 gene -506 insertion/deletion (I/D), factor V Leiden (FVL), prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with disease-free survival (DFS) in breast cancer.
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).
MDR analysis demonstrated a significant tri-variate interaction among RFC1 80, MTHFR 677 and TYMS 5'-UTR loci (P (trend) < 0.02) with high-risk genotype combination showing inflated risk for breast cancer (OR 4.65, 95% CI 1.77-12.24).
Therefore, our data do not support the hypothesis that genetic variation in the MTHFR gene is implicated in the aetiology of postmenopausal breast cancer.