title: Two-stage genome-wide association study identifies a novel susceptibility locus associated with melanoma.
abstract: Genome-wide association studies have identified 21 susceptibility loci associated with melanoma. These loci implicate genes affecting pigmentation, nevus count, telomere maintenance, and DNA repair in melanoma risk. Here, we report the results of a two-stage genome-wide association study of melanoma. The stage 1 discovery phase consisted of 4,842 self-reported melanoma cases and 286,565 controls of European ancestry from the 23andMe research cohort and the stage 2 replication phase consisted of 1,804 melanoma cases and 1,026 controls from the University of Texas M.D. Anderson Cancer Center. We performed a combined meta-analysis totaling 6,628 melanoma cases and 287,591 controls. Our study replicates 20 of 21 previously known melanoma-loci and confirms the association of the telomerase reverse transcriptase, TERT, with melanoma susceptibility at genome-wide significance. In addition, we uncover a novel polymorphism, rs187843643 (OR = 1.96; 95% CI = [1.54, 2.48]; P = 3.53 x 10-8), associated with melanoma. The SNP rs187842643 lies within a noncoding RNA 177kb downstream of BASP1 (brain associated protein-1). We find that BASP1 expression is suppressed in melanoma as compared with benign nevi, providing additional evidence for a putative role in melanoma pathogenesis.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Ransohoff
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
authors.forename: Wenting
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Hyunje G
authors.initials: HG
authors.lastname: Cho
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Harvind C
authors.initials: HC
authors.lastname: Chahal
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.|Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital and Institute, National Clinical Research Center for Cancer, Tianjin and Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Hong-Ji
authors.initials: HJ
authors.lastname: Dai
authors.affiliation: Department of 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: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jean Y
authors.initials: JY
authors.lastname: Tang
authors.affiliation: 23andMe Inc., Mountain View, CA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.affiliation: Department of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.affiliation: Duke Cancer Institute, Department of Medicine, Duke University, Durham, NC,USA.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Kavita Y
authors.initials: KY
authors.lastname: Sarin
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D019098:Telomerase / Q000235:genetics
chemical_list: C104089:BASP1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C509186:TERT protein, human; D019098:Telomerase
keywords: BASP1; genome-wide association study; melanoma; single nucleotide polymorphism; susceptibility loci