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Cancer Res. 2016 Jun 1;76(11):3277-84. doi: 10.1158/0008-5472.CAN-15-2564. Epub 2016 Mar 29.

Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3.

Author information

1
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.
2
Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Bio-X Institutes, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
3
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.
4
Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
5
Department of Urology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
6
Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China.
7
Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
8
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
9
Department of Urology, Jiangsu Province Hospital of TCM, Nanjing, China.
10
Department of Urology, The Huai-An First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
11
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
12
Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
13
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
14
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.
15
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.
16
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.

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.

PMID:
27206850
DOI:
10.1158/0008-5472.CAN-15-2564
[Indexed for MEDLINE]
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