全基因组关联研究在日本人群中确定了15号染色体长臂24区上与膀胱癌风险相关的单核苷酸多态性。
Genome-wide association study identified SNP on 15q24 associated with bladder cancer risk in Japanese population.
作者信息
Matsuda Koichi, Takahashi Atsushi, Middlebrooks Candace D, Obara Wataru, Nasu Yasutomo, Inoue Keiji, Tamura Kenji, Yamasaki Ichiro, Naya Yoshio, Tanikawa Chizu, Cui Ri, Figueroa Jonine D, Silverman Debra T, Rothman Nathaniel, Namiki Mikio, Tomita Yoshihiko, Nishiyama Hiroyuki, Kohri Kenjiro, Deguchi Takashi, Nakagawa Masayuki, Yokoyama Masayoshi, Miki Tsuneharu, Kumon Hiromi, Fujioka Tomoaki, Prokunina-Olsson Ludmila, Kubo Michiaki, Nakamura Yusuke, Shuin Taro
机构信息
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Center for Integrative Medical Science, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
出版信息
Hum Mol Genet. 2015 Feb 15;24(4):1177-84. doi: 10.1093/hmg/ddu512. Epub 2014 Oct 3.
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.
通过对总共1131例日本膀胱癌病例和12558例非癌症对照进行全基因组关联分析及独立重复研究，我们在15号染色体q24区域鉴定出一个易感位点。单核苷酸多态性（SNP）rs11543198与膀胱癌风险相关，比值比（OR）为1.41，P值为4.03×10⁻⁹。亚组分析显示，rs11543198在男性吸烟者中作用更强，OR为1.66。与rs11543198处于完全连锁不平衡状态（r² = 1）的SNP rs8041357，在欧洲人中也与膀胱癌风险相关（加性模型P = 0.045，隐性模型P = 0.025），尽管其在欧洲人中的次要等位基因频率（3.7%）远低于日本人（22.2%）。该区域的插补分析提示，代谢烟草衍生致癌物的CYP1A2是一个候选致病基因。我们还证实了先前报道的位点，即SLC14A1、APOBEC3A、PSCA和MYC与膀胱癌的关联。我们的发现表明基因变异在化学物质相关的膀胱癌发生发展中起关键作用。
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