Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung cancer patients treated with platinum-based therapy.
Abstract
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.
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https://hdl.handle.net/10161/17960Published Version (Please cite this version)
10.1038/s41598-017-10800-5Publication Info
Zhang, Ruoxin; Jia, Ming; Xue, Huijing; Xu, Yuan; Wang, Mengyun; Zhu, Meiling; ...
Wei, Qingyi (2017). Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung
cancer patients treated with platinum-based therapy. Scientific reports, 7(1). pp. 10702. 10.1038/s41598-017-10800-5. Retrieved from https://hdl.handle.net/10161/17960.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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