title: The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.
abstract: In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.
authors: Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7231, USA.
authors: Summer S
authors: SS
authors: Han
authors: Meredith
authors: M
authors: Yeager
authors: Lee E
authors: LE
authors: Moore
authors: Ming-Hui
authors: MH
authors: Wei
authors: Ruth
authors: R
authors: Pfeiffer
authors: Ousmane
authors: O
authors: Toure
authors: Mark P
authors: MP
authors: Purdue
authors: Mattias
authors: M
authors: Johansson
authors: Ghislaine
authors: G
authors: Scelo
authors: Charles C
authors: CC
authors: Chung
authors: Valerie
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authors: Gaborieau
authors: David
authors: D
authors: Zaridze
authors: Kendra
authors: K
authors: Schwartz
authors: Neonilia
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authors: Szeszenia-Dabrowska
authors: Faith
authors: F
authors: Davis
authors: Vladimir
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authors: Bencko
authors: Joanne S
authors: JS
authors: Colt
authors: Vladimir
authors: V
authors: Janout
authors: Vsevolod
authors: V
authors: Matveev
authors: Lenka
authors: L
authors: Foretova
authors: Dana
authors: D
authors: Mates
authors: M
authors: M
authors: Navratilova
authors: Paolo
authors: P
authors: Boffetta
authors: Christine D
authors: CD
authors: Berg
authors: Robert L
authors: RL
authors: Grubb
authors: Victoria L
authors: VL
authors: Stevens
authors: Michael J
authors: MJ
authors: Thun
authors: W Ryan
authors: WR
authors: Diver
authors: Susan M
authors: SM
authors: Gapstur
authors: Demetrius
authors: D
authors: Albanes
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Jarmo
authors: J
authors: Virtamo
authors: Laurie
authors: L
authors: Burdett
authors: Antonin
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authors: Brisuda
authors: James D
authors: JD
authors: McKay
authors: Joseph F
authors: JF
authors: Fraumeni
authors: Nilanjan
authors: N
authors: Chatterjee
authors: Philip S
authors: PS
authors: Rosenberg
authors: Nathaniel
authors: N
authors: Rothman
authors: Paul
authors: P
authors: Brennan
authors: Wong-Ho
authors: WH
authors: Chow
authors: Margaret A
authors: MA
authors: Tucker
authors: Stephen J
authors: SJ
authors: Chanock
authors: Jorge R
authors: JR
authors: Toro
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060148:HapMap Project; D006239:Haplotypes; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012907:Smoking; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1