Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas

Abstract

<b><i>Background:</i></b> We aimed to explore the relation of <i>XPD</i> and <i>XPF</i> variants with non-small cell lung cancer (NSCLC) risk and the effect of these variants on the sensitivity to cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas. <b><i>Methods:</i></b> Eight single-nucleotide polymorphisms (SNPs) in <i>XPD</i> and <i>XPF</i> were genotyped by Agena MassARRAY platform among 506 NSCLC cases and 510 healthy controls. Correlation of <i>XPD</i> and <i>XPF</i> gene polymorphisms with NSCLC susceptibility and the response of cis­platin-based chemotherapy were analyzed with logistic regression by calculating odds ratios (ORs) and 95% confidence intervals (CIs). <b><i>Results:</i></b> <i>XPD</i> rs13181 (OR = 1.53, 95% CI: 1.04–2.24, <i>p</i> = 0.029) and rs1052555 (OR = 1.63, 95% CI: 1.05–2.53, <i>p</i> = 0.029) possibly contributed to the increased risk of lung adenocarcinoma, while <i>XPD</i> rs238406 (OR = 0.63, 95% CI: 0.43–0.94, <i>p</i> = 0.024) was a protective factor for lung squamous cell carcinoma. Age, gender, BMI, smoking, and drinking might affect the correlation of <i>XPD</i> and <i>XPF</i> polymorphisms with NSCLC risk. More importantly, <i>XPD</i> rs13181 (OR = 2.91, <i>p</i> = 0.015), <i>XPD</i> rs1052555 (OR = 2.67, <i>p</i> = 0.022), and <i>XPF</i> rs231127 (OR = 4.15, <i>p</i> = 0.008) were associated with treatment response in NSCLC patients underwent cisplatin-based chemotherapy. <b><i>Conclusion:</i></b> This study found that <i>XPD</i> and <i>XPF</i> variants might contribute to NSCLC risk and the response of cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas.