Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung cancer patients treated with platinum-based therapy.

Published online

Journal Article

Nucleotide excision repair (NER) plays a vital role in platinum-induced DNA damage during chemotherapy. We hypothesize that regulatory single nucleotide polymorphisms (rSNPs) of the core NER genes modulate clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based chemotherapy (PBS). We investigated associations of 25 rSNPs in eight NER genes with progression free survival (PFS) and overall survival (OS) in 710 NSCLC patients. We found that ERCC1 rs3212924 AG/GG and XPC rs2229090 GC/CC genotypes were associated with patients' PFS (HRadj = 1.21, 95% CI = 1.03-1.43, P adj = 0.021 for ERCC1 and HRadj = 0.80, 95% CI = 0.68-0.94, P adj = 0.007 for XPC), compared with the AA and GG genotypes, respectively. The association of XPC rs2229090 was more apparent in adenocarcinoma than in squamous cell carcinoma patients. Additionally, ERCC4 rs1799798 GA/AA genotypes were associated with poorer OS (HRadj = 1.32, 95% CI = 1.04-1.69, P adj = 0.026), compared with the GG genotype. The expression quantitative trait loci analysis revealed that ERCC1 rs3212924 and XPC rs2229090 might regulate transcription of their genes, which is consistent with their associations with survival. Larger studies are needed to validate our findings with further functional studies to elucidate the mechanisms underlying these observed associations.

Full Text

Duke Authors

Cited Authors

  • Zhang, R; Jia, M; Xue, H; Xu, Y; Wang, M; Zhu, M; Sun, M; Chang, J; Wei, Q

Published Date

  • September 6, 2017

Published In

Volume / Issue

  • 7 / 1

Start / End Page

  • 10702 -

PubMed ID

  • 28878296

Pubmed Central ID

  • 28878296

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/s41598-017-10800-5

Language

  • eng

Conference Location

  • England