Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Background：Chemotherapy toxicity is a serious problem from which non-small cell lung cancer（NSCLC） patients suffer.The mismatch repair（MMR） system is associated with platinum-based chemotherapy toxicity in NSCLC patients.In this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.Methods：A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study.Toxicity was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.Results：MutS homolog 2[MSH2） rs6544991[odds ratio（OR） 2.98,95%confidence interval（CI） 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627（OR 2.38,95%CI 1.23-4.60,P = 0.010）,rs6151670（OR 2.05,95%CI 1.07-3.93,P = 0.031）,and rs7709909（OR 2.38,95%CI 1.23-4.64,P = 0.010）were associated with hematologic toxicity in the dominant model.Additionally,MSH5 rs805304 was significantly associated with overall toxicity（OR 2.21,95%CI 1.19-4.09,P = 0.012）,and M5H5 rs707939 was significantly associated with both overall toxicity（OR 0.42,95%CI 0.23-0.76,P = 0.004） and gastrointestinal toxicity（OR 0.44,95%CI 0.20-0.96,P = 0.038） in the dominant model.Conclusion：Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.