Common Variations of DNA Repair Genes are Associated with Response to Platinum-based Chemotherapy in NSCLCs


Aim: Individual differences in chemosensitivity and clinical outcome of non-small-cell lung cancer (NSCLC)patients may be induced by host inherited factors. We investigated the impact of XPD Arg156Arg, XPDAsp312Asn, XPD Asp711Asp and XPD Lys751Gln gene polymorphisms on the efficacy of platinum-basedchemotherapy in NSCLC patients.
Methods: A total of 496 were consecutively selected from the Affiliated Hospitalof Nantong University between Jan. 2003 and Nov. 2006, and all patients were followed-up until Nov. 2011.The genotyping of XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp and XPD Lys751Gln was conducted byduplex polymerase-chain-reaction with the confronting-two-pair primer methods.
Results: Individuals with XPD312 C/T+T/T and XPD 711 C/T+T/T exhibited poor responses to chemotherapy when compared with the wildtypegenotype, with adjusted ORs(95% CI) of 0.67(0.38-0.97) and 0.54(0.35-0.96), respectively. Cox regressionshowed the median PFS and OS of patients of XPD 312 C/T+T/T genotype and XPD 711 C/T+T/T genotype tobe significantly lower than those with wild-type homozygous genotype.
Conclusion: We found polymorphismsin XPD to be associated with response to platinum-based chemotherapy in NSCLC, and our findings provideinformation for therapeutic decisions for individualized therapy.