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Genetic variants in RORA and DNMT1 associated with cutaneous melanoma survival.

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Date
2018-06
Authors
Li, Bo
Wang, Yanru
Xu, Yinghui
Liu, Hongliang
Bloomer, Wendy
Zhu, Dakai
Amos, Christopher I
Fang, Shenying
Lee, Jeffrey E
Li, Xin
Han, Jiali
Wei, Qingyi
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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 article
Subject
Humans
Melanoma
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
Permalink
https://hdl.handle.net/10161/18513
Published Version (Please cite this version)
10.1002/ijc.31243
Publication 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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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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