MTHFR polymorphism as a predictive biomarker for gastrointestinal and hematological toxicity in North Indian...

In the present study, we investigated the relationship between the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and overall survival, toxicity and treatment response for North Indian adenocarcinoma patients. The polymorphisms of MTHFR gene in north Indian adenocarcinoma patients were assessed by PCR-RFLP. Our data observed that patients with mutant genotype (C/C) for 1298 A>C) polymorphism showed higher trend of median survival time compared to patients bearing the wild type genotype (A/A) (MST= 13.93 vs. 7.97, p=0.12). Further, we observed patients with the heterozygous genotype for A1298C polymorphism had 12-fold risk of diarrhea (AOR =12.54, 95% CI = 1.54-101.86, p=0.018). The patients with heterozygous genotype (CT) of the C677T polymorphism had 5.34-fold increased risk of developing neutropenia (AOR=5.34, 95% CI=1.49-19.06, p=0.009). Our results suggest that MTHFR polymorphisms are associated with hematological toxicity. MTHFR polymorphism might impact the development of pemetrexed and platinum-related toxicities but not as a clinical predictor of efficiency.