Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival.
Abstract
Cutaneous melanoma (CM) is considered as a steroid hormone-related malignancy. However,
few studies have evaluated the roles of genetic variants encoding steroid hormone
receptor genes and their related regulators (SHR-related genes) in CM-specific survival
(CMSS). Here, we performed a pathway-based analysis to evaluate genetic variants of
191 SHR-related genes in 858 CMSS patients using a dataset from a genome-wide association
study (GWAS) from The University of Texas MD Anderson Cancer Center (MDACC), and then
validated the results in an additional dataset of 409 patients from the Harvard GWAS.
Using multivariate Cox proportional hazards regression analysis, we identified three-independent
SNPs (RORA rs782917 G > A, RORA rs17204952 C > T and DNMT1 rs7253062 G > A) as predictors
of CMSS, with a variant-allele attributed hazards ratio (HR) and 95% confidence interval
of 1.62 (1.25-2.09), 1.60 (1.20-2.13) and 1.52 (1.20-1.94), respectively. Combined
analysis of risk genotypes of these three SNPs revealed a decreased CMSS in a dose-response
manner as the number of risk genotypes increased (ptrend < 0.001); however, no improvement
in the prediction model was observed (area under the curve [AUC] = 79.6-80.8%, p = 0.656),
when these risk genotypes were added to the model containing clinical variables. Our
findings suggest that genetic variants of RORA and DNMT1 may be promising biomarkers
for CMSS, but these results needed to be validated in future larger studies.
Type
Journal articleSubject
HumansMelanoma
Skin Neoplasms
Neoplasm Staging
Proportional Hazards Models
ROC Curve
Genotype
Polymorphism, Single Nucleotide
Alleles
Quantitative Trait Loci
Adult
Aged
Middle Aged
Female
Male
Genetic Variation
Genome-Wide Association Study
Nuclear Receptor Subfamily 1, Group F, Member 1
Kaplan-Meier Estimate
Biomarkers, Tumor
DNA (Cytosine-5-)-Methyltransferase 1
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https://hdl.handle.net/10161/18513Published Version (Please cite this version)
10.1002/ijc.31243Publication Info
Li, Bo; Wang, Yanru; Xu, Yinghui; Liu, Hongliang; Bloomer, Wendy; Zhu, Dakai; ...
Wei, Qingyi (2018). Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival. International journal of cancer, 142(11). pp. 2303-2312. 10.1002/ijc.31243. Retrieved from https://hdl.handle.net/10161/18513.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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