Single Nucleotide Polymorphisms And Genetic Susceptibility To Cancer

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in converting folate to methyl donor for DNA methylation, an epigenetic modification known to be dysregulated in carcinogenesis. This case-control study was designed to examine the association between MTHFR functional polymorphisms and susceptibility to cancers, including gastric cardiac adenocarcinoma (GCA), lung cancer, colorectal cancer (CRC), and breast cancer. The study subjects were 217 patients with GCA, 505 patients with lung cancer, 248 patients with CRC, 217 patients with breast cancer, 468 population-based controls for GCA, lung cancer and CRC and 218 female population-based controls for breast cancer. The MTHFR C677T and A1298C genotypes were detected by a polymerase chain reaction-based restriction fragment length polymorphism assay. It was found that subjects with the MTHFR 677TT genotype had a 2-fold increased risk of cancer [odds ratio (OR), 1.97; 95% confidence interval (CI), 1.44-2.68]. Moreover, a significantly elevated risk was also seen among the MTHFR 677CT heterozygotes, with the OR being 1.36 (95% CI, 1.04-1.76). About breast cancer, only subjects with the MTHFR 677TT genotype had an increased risk of cancer compared with 677CC genotype (OR, 1.84; 95% CI, 1.09-3.14). The MTHFR A1298C polymorphism had no effect on risk of all cancers, although it interacts with the C677T polymorphism. These findings demonstrated that the MTHFR polymorphisms might be determinants of common cancers among this at-risk Chinese population and provide important clues for genomic-based cancer prevention.