Format

Send to

Choose Destination
Int J Cancer. 2018 Jun 1;142(11):2303-2312. doi: 10.1002/ijc.31243. Epub 2018 Jan 17.

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

Li B1,2,3, Wang Y1,2, Xu Y1,2,4, Liu H1,2, Bloomer W1,2, Zhu D5, Amos CI5, Fang S6, Lee JE6, Li X7, Han J8, Wei Q1,2,9.

Author information

1
Duke Cancer Institute, Duke University Medical Center, Durham, NC.
2
Department of Medicine, Duke University School of Medicine, Durham, NC.
3
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
4
Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
5
Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH.
6
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
7
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
8
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
9
Department of Population Health Sciences, Duke University School of Medicine, Durham, NC.

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.

KEYWORDS:

cutaneous melanoma (CM); cutaneous melanoma-specific survival (CMSS); genome-wide association study (GWAS); single-nucleotide polymorphism (SNP); steroid hormone receptor

PMID:
29313974
PMCID:
PMC5893376
DOI:
10.1002/ijc.31243
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center