Abstract

Pharmacogenetics of DNA repair gene polymorphisms in non-small-cell lung carcinoma patients on platinum-based chemotherapy

Individual differences in chemosensitivity and clinical outcome of non-small-cell lung carcinoma (NSCLC) patients can be influenced by host-inherited factors. We investigated the impact of XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln, XPD Arg156Arg, XPD Asp312Asn, XPD Asp711Asp, and XPD Lys751Gln gene polymorphisms on treatment efficacy in 375 NSCLC patients on platinum-based chemotherapy. We also examined progression-free survival and overall survival. The gene polymorphisms were analyzed by duplex PCR. The patients with XRCC1 399A/A had a significantly better response to chemotherapy. Individuals with XPD 711 Asp and XPD 312 Asn alleles responded poorly to chemotherapy when compared with the wide-type genotype. The adjusted hazard ratio(HR) in the Cox regression model was calculated. The XRCC1 399A/A polymorphism was associated with better progression free survival and overall survival of NSCLC patients (HR=0.61 and 0.55). On the other hand, the XPD 711 Asp allele was associated with poorer progression free survival and overall survival compared to the C/C genotype, with HRs of 1.89 and 1.90. The XPD 312 Asn allele was found to be associated with non-significantly reduced survival of NSCLC patients (HR = 1.73). In conclusion, we found the polymorphisms of XRCC1 and XPD to be related to the efficacy of platinum-based chemotherapy in NSCLC patients. This information should aid in therapeutic decisions for individualized therapy in NSCLC cases.

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