Polymorphisms in nucleotide excision repair genes XPC and XPD and clinical responses to platinum-based chemotherapy in advanced non-small cell lung cancer

Objective: Nucleotide excision repair has been shown to have great impact on the sensitivity of tumors to platinum-based chemotherapy. This study was to examine the association between genetic polymorphisms in XPC and XPD, two important components in nucleotide excision repair system, and clinical response to platinum-based chemotherapy in advanced non-small cell lung cancer. Methods: Patients (n = 151) treated with platinum-based chemotherapy were genotyped for the AT dinucleotide insertion or deletion in intron 9 of XPC or Lys751 Gln polymorphism in XPD. Clinical response to chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model and adjusted for sex, age, clinical stage, and regime of chemotherapy. Results: The overall response rate to the chemotherapy (CR + PR) was 35.1%, with 1 CR, 52 PR, 75 SD, and 23 PD. It was found that patients with the XPC LL genotype had significantly higher response rate than patients with the XPC SS genotype (adjusted OR = 3.19, 95% CI = 1. 11-9. 17 ;P = 0.031). However, no association was found between the XPD Lys751 Gln polymorphism and response to the chemotherapy. In addition, these two polymorphisms seemed to have synergic effect, with the OR being 2.90 (95% CI = 1.07-7.86) for patients carrying the XPC LL and XPD Lys/Lys genotypes compared with those carrying the XPC SS or SL and XPD Lys/Lys genotypes. Conclusion: These results suggest that genetic polymorphisms in nucleotide excision repair might be associated with clinical response to platinum-based chemotherapy.