title: Genome-wide association study identifies novel loci predisposing to cutaneous melanoma.
abstract: We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. camos@mdanderson.org
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Wei V
authors.initials: WV
authors.lastname: Chen
authors.forename: Shenying
authors.initials: S
authors.lastname: Fang
authors.forename: Roman
authors.initials: R
authors.lastname: Kosoy
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Zhang
authors.forename: Abrar A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: Selina
authors.initials: S
authors.lastname: Vattathil
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Schacherer
authors.forename: Julie M
authors.initials: JM
authors.lastname: Gardner
authors.forename: Yuling
authors.initials: Y
authors.lastname: Wang
authors.forename: D Tim
authors.initials: DT
authors.lastname: Bishop
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Barrett
authors.forename: Stuart
authors.initials: S
authors.lastname: MacGregor
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: David L
authors.initials: DL
authors.lastname: Duffy
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: Anne
authors.initials: A
authors.lastname: Cust
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brown
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Grimm
authors.forename: Yaji
authors.initials: Y
authors.lastname: Xu
authors.forename: Younghun
authors.initials: Y
authors.lastname: Han
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Jing
authors.forename: Caitlin
authors.initials: C
authors.lastname: McHugh
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.forename: Kim F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Michael F
authors.initials: MF
authors.lastname: Seldin
authors.forename: Jiali
authors.initials: J
authors.lastname: Han
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D015201:Meta-Analysis as Topic; D010858:Pigmentation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D005819:Genetic Markers; D020662:Guanine Nucleotide Exchange Factors; C118566:HERC2 protein, human; D044767:Ubiquitin-Protein Ligases