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Association of polymorphisms in translesion synthesis genes with prognosis of advanced non‐small‐cell lung cancer patients treated with platinum‐based chemotherapy
Author(s) -
Zhang Xuelin,
Chen Qun,
Chen Jia,
He Chunya,
Mao Jianlin,
Dai Yuechu,
Yang Xi,
Hu Wei,
Zhu Chengchu,
Chen Baofu
Publication year - 2016
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24103
Subject(s) - cisplatin , single nucleotide polymorphism , lung cancer , oncology , chemotherapy , genotype , medicine , gene , cancer research , bioinformatics , biology , genetics
Background and Objectives Translesion synthesis (TLS) polymerases enable cells to bypass or overcome DNA damage during DNA replication and contributes to genomic instability and cancer. Inhibition of the expression of TLS genes enhances the sensitivity of cancer cells to cisplatin. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) in the TLS genes and clinical outcome of advanced non‐small‐cell lung cancer (NSCLC) patients treated with platinum‐based chemotherapy. Methods A total of 16 SNPs were genotyped and analyzed in 302 advanced NSCLC patients (discovery set), and the results were further validated in additional 428 NSCLC patients (validation set). Results Analyses revealed significant associations of two SNPs, rs3213801 and rs3792136, with overall survival, with the lowest combined P values of 0.003 and 0.016, respectively. These effects also remained in stratification analyses by clinical variables. Furthermore, the number of risk genotypes of the two SNPs showed a cumulative effect on overall survival ( P = 0.03). Conclusions Genetic polymorphisms in the TLS genes might serve as potential predictive biomarkers of prognosis of advanced NSCLC patients treated with platinum‐based chemotherapy. J. Surg. Oncol. 2016;113:17–23 . © 2015 Wiley Periodicals, Inc.