MTHFR, MTR, and MTRR polymorphisms in relation to p16INK4A hypermethylation in mucosa of patients with colorectal cancer.

摘要: We recently analyzed the hypermethylation status of p16INK4a (p16) gene promoter in normal-appearing mucosa obtained from patients with colorectal cancer. Hypermethylation p16 was associated reduced survival these patients. In present study, germ line polymorphisms folate- and methyl-associated genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) (MTRR), were same patient cohort to find a possible link between genetic variants hypermethylation. Genomic DNA extracted blood (n = 181) controls 300). Genotype analyses run on an ABI PRISM(®) 7900HT sequence-detection system (Applied Biosystems), using real-time polymerase chain reaction TaqMan chemistry. The results showed that genotype distributions control groups similar. No significant differences cancer-specific or disease-free stage I-III according polymorphic detected, nor any detected when subgrouped MTHFR MTR dichotomized by mucosa. However, MTRR 66 AA/AG genotypes found have significantly worse positive, compared negative, for (hazard ratio 2.7; 95% confidence interval 1.2-6.4; P 0.023). contrast, there no difference among GG stratified status. These indicate relationship germ-line mucosa, which may affect clinical outcome