Genetic Variants in the Vitamin D Pathway Genes VDBP and RXRA Modulate Cutaneous Melanoma Disease-Specific Survival.
Pigment Cell Melanoma Res. 2015 Nov 17. doi: 10.1111/pcmr.12437. [Epub ahead of print]
Yin J1,2,3,4, Liu H2,3, Yi X2,3, Wu W5, Amos CI6, Fang S7, Lee JE7, Han J5,8, Wei Q2,3.
1Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Ren-ai Road Industrial Park District, Suzhou, China.
2Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA.
3 Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
4 Department of Epidemiology and Biostatistics and MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
5 Department of Epidemiology, Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, 46202, USA.
6 Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, 03755, USA.
7 Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
8 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA.
Single nucleotide polymorphisms (SNPs) in the vitamin D pathway genes have been implicated in cutaneous melanoma (CM) risk, but their role in CM disease-specific survival (DSS) remains obscure.
We comprehensively analyzed the prognostic roles of 2,669 common SNPs in the vitamin D pathway genes using data from a published genome-wide association study (GWAS) at The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated the SNPs of interest in another GWAS from the Nurses' Health Study and Health Professionals Follow-up Study. Among the 2,669 SNPs, 203 were significantly associated with DSS in MDACC dataset (P<0.05 and false positive report probability<0.2), of which 18 were the tag SNPs. In the replication, 2 of these 18 SNPs showed nominal significance:
- the VDBP rs12512631 T>C was associated with a better DSS [combined hazards ratio (HR)=0.66]; and the same for
- RXRA rs7850212 C>A (combined HR=0.38),
which were further confirmed by the Fine and Gray competing risks regression model. Further bioinformatics analyses indicated that these loci may modulate corresponding gene methylation status.
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