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

dc.contributor.author Wei, Qingyi
dc.contributor.author Zhang, Ruoxin
dc.contributor.author Jia, Ming
dc.contributor.author Xue, Huijing
dc.contributor.author Xu, Yuan
dc.contributor.author Wang, Mengyun
dc.contributor.author Zhu, Meiling
dc.contributor.author Sun, Menghong
dc.contributor.author Chang, Jianhua
dc.date.accessioned 2019-02-01T15:00:27Z
dc.date.available 2019-02-01T15:00:27Z
dc.date.issued 2017-09-06
dc.identifier 10.1038/s41598-017-10800-5
dc.identifier.issn 2045-2322
dc.identifier.issn 2045-2322
dc.identifier.uri https://hdl.handle.net/10161/17960
dc.description.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.
dc.language eng
dc.publisher Springer Nature
dc.relation.ispartof Scientific reports
dc.relation.isversionof 10.1038/s41598-017-10800-5
dc.title Genetic variants in ERCC1 and XPC predict survival outcome of non-small cell lung cancer patients treated with platinum-based therapy.
dc.type Journal article
duke.contributor.id Wei, Qingyi|0632334
dc.date.updated 2019-02-01T15:00:25Z
pubs.begin-page 10702
pubs.issue 1
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 7
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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