A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.

TitleA genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23.
Publication TypeJournal Article
Year of Publication2012
AuthorsWu X, Scelo G, Purdue MP, Rothman N, Johansson M, Ye Y, Wang Z, Zelenika D, Moore LE, Wood CG, Prokhortchouk E, Gaborieau V, Jacobs KB, Chow W-H, Toro JR, Zaridze D, Lin J, Lubinski J, Trubicka J, Szeszenia-Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Mates D, Jinga V, Bencko V, Slamova A, Holcatova I, Navratilova M, Janout V, Boffetta P, Colt JS, Davis FG, Schwartz KL, Banks RE, Selby PJ, Harnden P, Berg CD, Hsing AW, Grubb RL, Boeing H, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, Duell EJ, Quirós J R, Sanchez M-J, Navarro C, Ardanaz E, Dorronsoro M, Khaw K-T, Allen NE, Bueno-de-Mesquita BH, Peeters PHM, Trichopoulos D, Linseisen J, Ljungberg B, Overvad K, Tjønneland A, Romieu I, Riboli E, Stevens VL, Thun MJ, Diver RW, Gapstur SM, Pharoah PD, Easton DF, Albanes D, Virtamo J, Vatten L, Hveem K, Fletcher T, Koppova K, Cussenot O, Cancel-Tassin G, Benhamou S, Hildebrandt MA, Pu X, Foglio M, Lechner D, Hutchinson A, Yeager M, Fraumeni JF, Lathrop M, Skryabin KG, McKay JD, Gu J, Brennan P, Chanock SJ
JournalHum Mol Genet
Date Published2012 Jan 15
KeywordsCarcinoma, Renal Cell, Chromosomes, Human, Pair 12, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Neoplasms

Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

Alternate JournalHum. Mol. Genet.
PubMed ID22010048