title: Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.
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.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Center for Integrative Medical Science, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Candace D
authors.initials: CD
authors.lastname: Middlebrooks
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Obara
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Koichi, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Koichi, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Koichi, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamasaki
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naya
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Tanikawa
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Ri
authors.initials: R
authors.lastname: Cui
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Jonine D
authors.initials: JD
authors.lastname: Figueroa
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.affiliation: Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Department of Urology, Faculty of Medicine, University of Tsukuba, Ibaragi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.affiliation: Department of Urology, Graduate School of Medicine, Gifu University, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Urology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yokoyama
authors.affiliation: Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kumon
authors.affiliation: Department of Urology, Iwate Medical University School of Medicine, Iwate, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Prokunina-Olsson
authors.affiliation: Center for Integrative Medical Science, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Medicine and Department of Surgery, Center for Personalized Therapeutics, The University of Chicago, Chicago, IL, USA ynakamura@bsd.uchicago.edu.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Urology, School of Medicine, Kochi University, Koichi, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002884:Chromosomes, Human, Pair 15; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012907:Smoking; D001749:Urinary Bladder Neoplasms / Q000235:genetics*