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

dc.contributor.author

Zhang, Ruoxin

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Jia, Ming

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Xue, Huijing

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Xu, Yuan

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Wang, Mengyun

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Zhu, Meiling

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Sun, Menghong

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Chang, Jianhua

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Wei, Qingyi

dc.date.accessioned

2019-02-01T15:00:27Z

dc.date.available

2019-02-01T15:00:27Z

dc.date.issued

2017-09-06

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2019-02-01T15:00:25Z

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.identifier

10.1038/s41598-017-10800-5

dc.identifier.issn

2045-2322

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2045-2322

dc.identifier.uri

https://hdl.handle.net/10161/17960

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

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Scientific reports

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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.orcid

Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

pubs.begin-page

10702

pubs.issue

1

pubs.organisational-group

School of Medicine

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Population Health Sciences

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Basic Science Departments

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Medicine, Medical Oncology

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Medicine

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Clinical Science Departments

pubs.publication-status

Published

pubs.volume

7

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