Analysis of polymorphic loci in ERCC and XRCC family in Korean non-small cell lung carcinoma patients

초록

Polymorphisms present in ERCC and XRCC DNA repair genes have been postulated to serve as possible prognosis markers for cancer therapy as well as implicated in the genetic susceptibility to various forms of cancer. This study was conducted to probe their possible roles in therapeutic outcomes with DNA damaging chemotherapeutic modalities. Ninety-one non-small cell lung carcinoma (NSCLC) patients treated with cisplatin plus gemcitabine or paclitaxel were analyzed for the presence of polymorphisms on ERCC1 N118N, ERCC2 K751Q, ERCC2 D312N, ERCC4 P379S, XRCC1 R280H and XRCC3 T241M loci by SNaPshot method. Treatment response showed not statistical significant difference according to the polymorphisms of ERCC1 N118N, ERCC2 K751Q, D312N, XRCC1 R280H and XRCC3 T241M. Interestingly, when ERCC1 N118N and XRCC1 R280H variability were analyzed among patients for the therapeutic outcome via Cox proportional hazard model, the presence of wild type (CC) in ERCC1 N118N was found to be correlated with a better prognosis as judged by one year survival (p=0.0923). The one-year survival was 21% in patients with wild type (CC) while 4.3% in patients with C to T transition (CT, TT). We are currently evaluating other polymorphic loci in ERCC1 to probe a possible correlation with genetic susceptibility to lung cancer and/or with the therapeutic outcome. To our knowledge, this is the first report on the polymorphic profiles of ERCC and XRCC DNA repair genes in Korean non-small cell lung carcinoma patients.