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. 2015 Feb 15;24(4):1177-84.
doi: 10.1093/hmg/ddu512. Epub 2014 Oct 3.

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

Koichi Matsuda  1 , Atsushi Takahashi  2 , Candace D Middlebrooks  3 , Wataru Obara  4 , Yasutomo Nasu  5 , Keiji Inoue  6 , Kenji Tamura  6 , Ichiro Yamasaki  6 , Yoshio Naya  7 , Chizu Tanikawa  1 , Ri Cui  1 , Jonine D Figueroa  3 , Debra T Silverman  3 , Nathaniel Rothman  3 , Mikio Namiki  8 , Yoshihiko Tomita  9 , Hiroyuki Nishiyama  10 , Kenjiro Kohri  11 , Takashi Deguchi  12 , Masayuki Nakagawa  13 , Masayoshi Yokoyama  14 , Tsuneharu Miki  7 , Hiromi Kumon  5 , Tomoaki Fujioka  4 , Ludmila Prokunina-Olsson  3 , Michiaki Kubo  2 , Yusuke Nakamura  15 , Taro Shuin  6
Affiliations

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

Koichi Matsuda et al. Hum Mol Genet. .

Abstract

Through genome-wide association analysis and an independent replication study using a total of 1131 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 × 10(-9). Subgroup analysis revealed rs11543198 to have a stronger effect in male smokers with OR of 1.66. 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 minor allele frequency in Europeans (3.7%) compared with the Japanese (22.2%). 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. Our finding implies the crucial roles of genetic variations on the chemically associated development of bladder cancer.

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Figures

Figure 1.
Figure 1.
Manhattan plot showing the genome-wide P-values of association. The P-values were calculated by Cochran–Armitage trend test. The y-axis represents the −log10 P-values of 554 389 SNPs, and x-axis shows their chromosomal positions. The horizontal blue line shows the threshold of P ≤ 5 × 10−5 for selecting 84 SNPs for replication analysis.
Figure 2.
Figure 2.
Regional association plots around rs11543198 on 15q24 (1.4 Mb). Upper panel: P-values of genotyped SNPs (circle) and imputed SNPs (cross) are plotted (as −log10 P-value) against their physical position on chromosome 15 (NCBI Build 36). SNP rs11543198 is represented by purple circle. The genetic recombination rates estimated from 1000 Genomes samples (JPT + CHB) are shown with a blue line. SNP's color indicates LD with rs11543198 according to a scale from r2 = 0 to 1 based on pair-wise r2-values from HapMap JPT. Lower panel; gene annotations from the University of California Santa Cruz genome browser.
See this image and copyright information in PMC

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