This meta-analysis suggests that MTHFRC677T polymorphism is associated with decreased risk of colorectal cancer in East Asians, and MTHFR 677T variant has a protective effect on colorectal cancer.
The MTHFR 677T allele is associated with a lower risk of colorectal cancer in Asian populations, and there is effect modification by population plasma folate.
We evaluated the associations between plasma folate, MTHFRC677T, and A1298C, and colorectal cancer in three large prospective studies: the Nurses' Health Study, the Health Professionals Follow-up Study, and the Physicians' Health Study.
In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFRC667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR = 0.82, 95 % CI = 0.69-0.97; for TT vs. CT/CC: OR = 0.81, 95 % CI = 0.74-0.90).
Factor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study.
In conclusion, subjects with the variant MTHFR 677TT genotype appeared to have a significantly lower risk for colorectal cancer than those with the MTHFR 677CC genotype, and the methylation status of circulating p73 genomic DNA was substantially altered by the plasma folate level.
We found that the 677 C>T polymorphism in the MTHFR gene significantly decreased the risk for colorectal cancer in homozygous carriers of the variant allele (OR, 0.58; 95% CI, 0.39-0.87).
Compared with the MTHFR 677CC and MTHFR 1298 AA genotypes, for individuals who carried both MTHFR 677CC and 1298CC genotypes, the OR of colorectal cancer was 0.103 (95%CI = 0.012-0.900); among individuals who carried both MTHFR 677TT and 1298AC genotypes, the OR for risk of colorectal cancer was 0.169 (95%CI = 0.044-0.654).
However, in meta-analyses odds ratio for MTHFR c.677C>T homozygotes versus noncarriers were 1.07 (95% CI: 1.01-1.12) for any cancer, 1.77 (1.17-2.68) for esophagus cancer, 1.40 (1.19-1.66) for gastric cancer and 0.85 (0.77-0.94) for colorectal cancer.
Although MTHFRC677T was associated with increased risks of colorectal cancer, leukemia, and gastric cancer, our pooled data suggest no evidence for a major role of MTHFR C677T in the carcinogenesis of childhood acute lymphoblastic leukemia.
Collectively, these exploratory data provide suggestive evidence for the association of MTHFR 429 Ala/ Ala and TCN2 259 Arg/Arg and CIMP status in colorectal cancer.
We related prediagnostic plasma folate, vitamin B12, and total homocysteine concentrations, and the MTHFR 677C>T and 1298A>C polymorphisms, to the risk of colorectal cancer with and without the CpG island methylator phenotype (CIMP).
Association of polymorphisms MTHFRC677T and A1298C with risk of colorectal cancer, genetic and epigenetic characteristic of tumors, and response to chemotherapy.