TY - JOUR
T1 - Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population
AU - Matsuda, Koichi
AU - Takahashi, Atsushi
AU - Middlebrooks, Candace D.
AU - Obara, Wataru
AU - Nasu, Yasutomo
AU - Inoue, Keiji
AU - Tamura, Kenji
AU - Yamasaki, Ichiro
AU - Naya, Yoshio
AU - Tanikawa, Chizu
AU - Cui, Ri
AU - Figueroa, Jonine D.
AU - Silverman, Debra T.
AU - Rothman, Nathaniel
AU - Namiki, Mikio
AU - Tomita, Yoshihiko
AU - Nishiyama, Hiroyuki
AU - Kohri, Kenjiro
AU - Deguchi, Takashi
AU - Nakagawa, Masayuki
AU - Yokoyama, Masayoshi
AU - Miki, Tsuneharu
AU - Kumon, Hiromi
AU - Fujioka, Tomoaki
AU - Prokunina-Olsson, Ludmila
AU - Kubo, Michiaki
AU - Nakamura, Yusuke
AU - Shuin, Taro
N1 - Funding Information:
This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government. The work was supported in part by the Intramural Research Program (IRP) of the National Cancer Institute of the US National Institutes of Health.
Funding Information:
Characteristics of each cohort are shown in Supplementary Material, Table S1. In this study, we conducted GWAS and replication analyses using a total of 1131 bladder cancer cases and 12 558 controls. Case samples in GWAS and replication were obtained from a collaboration network consisting of Iwate Medical University, Okayama University, Kochi Medical School, Kyoto Prefectural University of Medicine, Kanazawa University, Yamagata University, University of Tsukuba, Nagoya City University, Gifu University, Kagoshima University and Ehime University. Control samples in GWAS and replication consisted of healthy volunteers (n ¼ 1919) and subjects with other diseases (n ¼ 10 639, cerebral aneurysm, chronic obstructive pulmonary disease, glaucoma, nephrolithiasis, nephrotic syndrome, epilepsy, atopic dermatitis and Grave’s disease) obtained from Biobank Japan Project supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan. In the BioBank Japan Project, DNA and serum of patients were collected through a collaborating network of 66 hospitals throughout Japan. More than 200 000 individuals with 47 common diseases, irrespective of prior treatment, were enrolled in this project from 2003. A list of participating hospitals is provided at the BioBank Japan website (http://www.biobankjp.org/english/index.html). Subjects with a history of any cancers were excluded from controls. Smoking information of both cases and controls was obtained by oral interview. This project was approved by the ethical committees at each institute.
Publisher Copyright:
© The Author 2014. Published by Oxford University Press. All rights reserved.
PY - 2015/2/15
Y1 - 2015/2/15
N2 - 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.
AB - 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.
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U2 - 10.1093/hmg/ddu512
DO - 10.1093/hmg/ddu512
M3 - Article
C2 - 25281661
AN - SCOPUS:84922455874
SN - 0964-6906
VL - 24
SP - 1177
EP - 1184
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 4
ER -
