Association between genetic variation within vitamin D receptor-DNA binding sites and risk of basal cell carcinoma.
An increasing number of studies have reported a protective association between vitamin D and cancer risk. The vitamin D endocrine system regulates transcriptional programs involved in inflammation, cell growth and differentiation through the binding of vitamin D receptor (VDR) to specific VDR elements. However, limited attention has been given to the role of variation within VDR binding sites in the development of basal cell carcinoma (BCC). Across 2,776 previously identified VDR binding sites, we identified 2,540 independent single-nucleotide polymorphisms (SNPs) and examined their associations with BCC risk in a genome-wide association meta-analysis totaling 17,187 BCC cases and 287,054 controls from two data sets. After multiple testing corrections, we identified two SNPs at new loci (rs16917546 at 10q21.1: odds ratio (OR) = 1.06, p = 3.16 × 10-7and rs79824801 at 12q13.3: OR = 1.10, p = 1.88 × 10-5) for the first time as independently related to BCC risk in meta-analysis; and both SNPs were nominally significant in two data sets. In addition, the SNP rs3769823 within VDR binding site at a previously reported BCC susceptibility locus (2q33.1, rs13014235) also exhibited a significant association (OR = 1.12, p = 3.99 × 10-18). A mutually adjusted model suggested that rs3769823 explained the signal in this region. Our findings support the hypothesis that inherited common variation in VDR binding sites affects the development of BCC.
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Yuan
Y
Lin
Department of Dermatology, Stanford University School of Medicine, Stanford, CA.
Harvind S
HS
Chahal
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Wenting
W
Wu
Department of Dermatology, Stanford University School of Medicine, Stanford, CA.
Hyunje G
HG
Cho
Department of Dermatology, Stanford University School of Medicine, Stanford, CA.
Katherine J
KJ
Ransohoff
Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Hongji
H
Dai
Department of Dermatology, Stanford University School of Medicine, Stanford, CA.
Jean Y
JY
Tang
Department of Dermatology, Stanford University School of Medicine, Stanford, CA.
Kavita Y
KY
Sarin
Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Jiali
0000-0002-1949-4907
J
Han
D000328:Adult; D000368:Aged; D001665:Binding Sites / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014807:Vitamin D / Q000378:metabolism
D018167:Receptors, Calcitriol; D014807:Vitamin D
basal cell carcinoma; genetic susceptibility; single nucleotide polymorphism; vitamin D receptor-DNA binding site