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Polymorphisms of nucleotide excision repair genes predict melanoma survival.

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Date
2013-07
Authors
Li, Chunying
Yin, Ming
Wang, Li-E
Amos, Christopher I
Zhu, Dakai
Lee, Jeffrey E
Gershenwald, Jeffrey E
Grimm, Elizabeth A
Wei, Qingyi
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Abstract
Melanoma is the most highly malignant skin cancer, and nucleotide excision repair (NER) is involved in melanoma susceptibility. In this analysis of 1,042 melanoma patients, we evaluated whether genetic variants of NER genes may predict survival outcome of melanoma patients. We used genotyping data of 74 tagging single-nucleotide polymorphisms (tagSNPs) in eight core NER genes from our genome-wide association study (including two in XPA, 14 in XPC, three in XPE, four in ERCC1, 10 in ERCC2, eight in ERCC3, 14 in ERCC4, and 19 in ERCC5) and evaluated their associations with prognosis of melanoma patients. Using the Cox proportional hazards model and Kaplan-Meier analysis, we found a predictive role of XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871 SNPs in the prognosis of melanoma patients (rs28720291: AG vs. GG, adjusted hazard ratio (adjHR)=11.2, 95% confidence interval (CI) 3.04-40.9, P=0.0003; rs4150314: AG vs. GG, adjHR=4.76, 95% CI 1.09-20.8, P=0.038; rs2470458: AA vs. AG/GG, adjHR=2.11, 95% CI 1.03-4.33, P=0.040; and rs50871: AA vs. AC/CC adjHR=2.27, 95% CI 1.18-4.35, P=0.015). Patients with an increasing number of unfavorable genotypes had markedly increased death risk. Genetic variants of NER genes, particularly XPE rs28720291, ERCC5 rs4150314, XPC rs2470458, and ERCC2 rs50871, may independently or jointly modulate survival outcome of melanoma patients. Because our results were based on a median follow-up of 3 years without multiple test corrections, additional large prospective studies are needed to confirm our findings.
Type
Journal article
Subject
Humans
Melanoma
Skin Neoplasms
Xeroderma Pigmentosum
Endonucleases
DNA-Binding Proteins
Nuclear Proteins
Transcription Factors
Prognosis
Survival Rate
Proportional Hazards Models
DNA Repair
Genotype
Polymorphism, Single Nucleotide
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Xeroderma Pigmentosum Group D Protein
Genome-Wide Association Study
Young Adult
Kaplan-Meier Estimate
Permalink
https://hdl.handle.net/10161/17991
Published Version (Please cite this version)
10.1038/jid.2012.498
Publication Info
Li, Chunying; Yin, Ming; Wang, Li-E; Amos, Christopher I; Zhu, Dakai; Lee, Jeffrey E; ... Wei, Qingyi (2013). Polymorphisms of nucleotide excision repair genes predict melanoma survival. The Journal of investigative dermatology, 133(7). pp. 1813-1821. 10.1038/jid.2012.498. Retrieved from https://hdl.handle.net/10161/17991.
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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Scholars@Duke

Wei

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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