Polymorphisms of nucleotide excision repair genes predict melanoma survival.
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 articleSubject
HumansMelanoma
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/10161/17991Published Version (Please cite this version)
10.1038/jid.2012.498Publication 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.
Collections
More Info
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

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info