We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.

Original publication

DOI

10.1038/ng.723

Type

Journal article

Journal

Nature genetics

Publication Date

01/2011

Volume

43

Pages

60 - 65

Addresses

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, USA.

Keywords

Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 11, Humans, Carcinoma, Renal Cell, Kidney Neoplasms, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Genome, Human, Genome-Wide Association Study