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

作者：Wu Xifeng^*; Scelo Ghislaine; Purdue Mark P; Rothman Nathaniel; Johansson Mattias; Ye Yuanqing; Wang Zhaoming; Zelenika Diana; Moore Lee E; Wood Christopher G; Prokhortchouk Egor; Gaborieau Valerie; Jacobs Kevin B; Chow Wong Ho; Toro Jorge R; Zaridze David; Lin Jie; Lubinski Jan; Trubicka Joanna; Szeszenia Dabrowska Neonilia; Lissowska Jolanta; Rudnai Peter; Fabianova Eleonora; Mates Dana; Jinga Viorel; Bencko Vladimir; Slamova Alena; Holcatova Ivana

来源：Human Molecular Genetics, 2012, 21(2): 456-462.

DOI：10.1093/hmg/ddr479

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%26apos; = 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 x 10(-10) and P = 6.07 x 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.

• 出版日期2012-1-15
• 单位NIH