title: Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3.
abstract: Genome-wide association studies (GWAS) of bladder cancer have identified a number of susceptibility loci in European populations but have yet to uncover the genetic determinants underlying bladder cancer incidence among other ethnicities. Therefore, we performed the first GWAS in a Chinese cohort comprising 3,406 cases of bladder cancer and 4,645 controls. We identified a new susceptibility locus for bladder cancer at 5q12.3, located in the intron of CWC27 (rs2042329), that was significantly associated with disease risk (OR = 1.40; P = 4.61 × 10(-11)). However, rs2042329 was not associated with bladder cancer risk in patients of European descent. The rs2042329 risk allele was also related to significantly increased expression levels of CWC27 mRNA and protein in bladder cancer tissues from Chinese patients. Additional functional analyses suggested that CWC27 played an oncogenic role in bladder cancer by inducing cell proliferation and suppressing apoptosis. In conclusion, the identification of a risk-associated locus at 5q12.3 provides new insights into the inherited susceptibility to bladder cancer in Chinese populations and may help to identify high-risk individuals. Cancer Res; 76(11); 3277-84. ©2016 AACR.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chu
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Chuanliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Mulong
authors.initials: M
authors.lastname: Du
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Changjun
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Xia
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, Jiangsu Province Hospital of TCM, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Urology, The Huai-An First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Tong
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Shen
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina. Program for Personalized Cancer Care, NorthShore University HealthSystem, Evanston, Illinois. drzdzhang@njmu.edu.cn shiyongyong@gmail.com jxu@wfubmc.edu.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Qingdao University, Qingdao, China. Department of Psychiatry, The First Teaching Hospital of Xinjiang Medical University, Urumqi, China. Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China. Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China. drzdzhang@njmu.edu.cn shiyongyong@gmail.com jxu@wfubmc.edu.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China. drzdzhang@njmu.edu.cn shiyongyong@gmail.com jxu@wfubmc.edu.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D015331:Cohort Studies; D021983:Cyclophilins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C000600171:Cwc27 protein, human; D021983:Cyclophilins