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

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 NakagawaMasayoshi Yokoyama, Tsuneharu Miki, Hiromi Kumon, Tomoaki Fujioka, Ludmila Prokunina-Olsson, Michiaki Kubo, Yusuke Nakamura, Taro Shuin

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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 (r2 = 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.

Original languageEnglish
Article numberddu512
Pages (from-to)1177-1184
Number of pages8
JournalHuman molecular genetics
Volume24
Issue number4
DOIs
Publication statusPublished - 15-02-2015

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Matsuda, K., Takahashi, A., Middlebrooks, C. D., Obara, W., Nasu, Y., Inoue, K., Tamura, K., Yamasaki, I., Naya, Y., Tanikawa, C., Cui, R., Figueroa, J. D., Silverman, D. T., Rothman, N., Namiki, M., Tomita, Y., Nishiyama, H., Kohri, K., Deguchi, T., ... Shuin, T. (2015). Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population. Human molecular genetics, 24(4), 1177-1184. [ddu512]. https://doi.org/10.1093/hmg/ddu512