The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma.

Authors

Han SS, Yeager M, Moore LE, Wei MH, Pfeiffer R, Toure O, Purdue MP, Johansson M, Scelo G, Chung CC, Gaborieau V, Zaridze D, Schwartz K, Szeszenia-Dabrowska N, Davis F, Bencko V, Colt JS, Janout V, Matveev V, Foretova L, ...show more Mates D, Navratilova M, Boffetta P, Berg CD, Grubb RL, Stevens VL, Thun MJ, Diver WR, Gapstur SM, Albanes D, Weinstein SJ, Virtamo J, Burdett L, Brisuda A, McKay JD, Fraumeni JF, Chatterjee N, Rosenberg PS, Rothman N, Brennan P, Chow WH, Tucker MA, Chanock SJ, Toro JR

Affiliations

• Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7231, USA.

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.