title: Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival.
abstract: 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 2669 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 2669 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, two 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.
authors.affiliation: Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.|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.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yi
authors.affiliation: Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Community and Family Medicine, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Shenying
authors.initials: S
authors.lastname: Fang
authors.affiliation: Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Epidemiology, Fairbanks School of Public Health, Indiana University Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.|Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D047490:Retinoid X Receptor alpha / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality; D015996:Survival Rate; D014809:Vitamin D-Binding Protein / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D047490:Retinoid X Receptor alpha; D014809:Vitamin D-Binding Protein
keywords: Cox regression; cutaneous melanoma; disease-specific survival; single nucleotide polymorphisms; vitamin D pathway