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.

Characterization of the nucleotide excision repair pathway and evaluation of compounds for overcoming the cisplatin resistance of non‑small cell lung cancer cell lines

“…In the present study, XPD silencing enhanced cisplatin sensitivity, and the XPF and XPD gene expression levels correlated with cisplatin resistance in NSCLC cell lines. Consequently, the results of the present study supported the findings of the clinical study of Li et al (34), and suggested that these molecules may be utilized as biomarkers for predicting cisplatin sensitivity.…”

“…Recently, Jian et al (33) reported that XPD overexpression significantly increased cisplatin sensitivity, and revealed that XPD regulated the PI3K/AKT signaling pathway in esophageal squamous cell carcinoma, this information also being valuable for the further evaluation of cisplatin resistance. However, Li et al (34) reported that XPD and XPF polymorphisms may contribute to the risk of NSCLC and the response to cisplatin-based chemotherapy in a Chinese population. In the present study, XPD silencing enhanced cisplatin sensitivity, and the XPF and XPD gene expression levels correlated with cisplatin resistance in NSCLC cell lines.…”