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Genome wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.

By: Koichi Matsuda, Atsushi Takahashi, Candace D Middlebrooks, Wataru Obara, Yasutomo Nasu, Keiji Inoue, Kenji Tamura, Ichiro Yamasaki, Yoshio Naya, Chizu Tanikawa, Ri Cui, Jonine D Figueroa, Debra T Silverman, Nathaniel Rothman, Mikio Namiki, Yoshihiko Tomita, Hiroyuki Nishiyama, Kenjiro Kohri, Takashi Deguchi, Masayuki Nakagawa, Masayoshi Yokoyama, Tsuneharu Miki, Hiromi Kumon, Tomoaki Fujioka, Ludmila Prokunina-Olsson, Michiaki Kubo, Yusuke Nakamura, Taro Shuin

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
2014-10-5; doi: 10.1093/hmg/ddu512

Abstract

Through genome wide association analysis and an independent replication study using a total of 1,131 bladder cancer cases and 12,558 non-cancer controls of Japanese populations, we identified a susceptibility locus on chromosome 15q24. SNP rs11543198 was associated with bladder cancer risk with odds ratio (OR) of 1.41 and P value of 4.03 x 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. Imputational analysis in this region suggested CYP1A2, which metabolizes tobacco-derived carcinogen, as a causative candidate gene. We also confirmed the association of previously-reported loci, namely SLC14A1, APOBEC3A, PSCA, and MYC, with bladder cancer. SNP rs8041357, which is in complete linkage disequilibrium (r(2)=1) with rs11543198, was also associated with bladder cancer risk in Europeans (P=0.045 for an additive and P=0.025 for a recessive model), despite much lower MAF in Europeans (3.7%) compared to the Japanese (22.2%). Our finding implies the crucial roles of genetic variations on the chemically-associated development of bladder cancer.