Association of Folate and Vitamins Involved in the 1-Carbon Cycle with Polymorphisms in the Methylenetetrahydrofolate Reductase Gene (MTHFR) and Global DNA Methylation in Patients with Colorectal Cancer.
Databases, including Medline, EMBASE, Cochrane and Chinese databases (including CNKI, Wanfang and VIP), were searched to identify the relevant articles describing MTHFR polymorphisms in patients with CRC.
MTHFRrs1801133 T allele serves as a predictive marker for CRC risk and future studies with larger samples and functional evaluation are warranted to validate the current findings.
Relevance of methylenetetrahydrofolate reductase gene variants C677T and A1298C with response to fluoropyrimidine-based chemotherapy in colorectal cancer: a systematic review and meta-analysis.
Analyses of KRAS mutations in metastatic colorectal cancer, EGFR mutations in advanced non-small cell lung cancer, CYP2D6 polymorphism in breast cancer, DPD polymorphism in colorectal cancer and MTHFR polymorphism in osteosarcoma have been performed by real time polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP).
Never/occasional consumers of alcohol with the MTHFRrs1801133 CT/TT genotype were also at a reduced risk of CRC compared to never/occasional drinkers with the CC genotype (OR = 0.68, 95% CI, 0.47-0.98) (P for interaction = 0.27).
MTHFR 677 homozygous TT genotype was protective (p <05) for CRC for all included populations; however, with heterogeneity across various racial-ethnic groups and opposing findings, it was a risk genotype for the subgroup of Hispanics (p <01).
In summary, this meta-analysis suggests that MTHFRA1298C polymorphism is associated with increased cervical cancer and lymphoma risk in Asians, and MTHFRA1298C polymorphism is associated with decreased colorectal cancer risk in Asians.
Pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated to assess the association of MTHFRC677T with the susceptibility to CRC.
In summary, this meta-analysis suggests that MTHFRC677T polymorphism is associated with increased breast cancer, gastric cancer, and hepatocellular cancer risk in Asians, is associated with increased gastric cancer, multiple myeloma, and NHL risk in Caucasians, is associated with decreased AALL risk in Caucasians, is associated with decreased CALL risk in Asians, is associated with increased breast cancer risk in Asians, is associated with decreased colon cancer risk, and is associated with decreased colorectal cancer risk in male population.
The distribution of MTHFRA1298C genotypes was similar in our CRC and in the HapMap Asian population, but was different from that in the White population.
5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1).
The current data suggest strong associations between both SNPs of germ-line MTHFR 677 C>T and 1298 A>C genotypes and CRC susceptibility in the Turkish population.
Our findings provide empirical evidence that MTHFR genetic polymorphisms may decrease the toxicity of irinotecan-based chemotherapy and increase the clinical benefits for CRC patients.