Research Papers:
A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population
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Abstract
Jacek Marzec1,*, Xueying Mao1,*, Meiling Li2,*, Meilin Wang3,*, Ninghan Feng4,5,*, Xin Gou6,*, Guomin Wang7,*, Zan Sun8,*, Jianfeng Xu9,10,*, Hua Xu11,*, Xiaoping Zhang12,*, Shan-Chao Zhao13, Guoping Ren14, Yongwei Yu15, Yudong Wu16, Ji Wu17, Yao Xue3, Bo Zhou18, Yanling Zhang14, Xingxing Xu2, Jie Li6, Weiyang He6, Sara Benlloch19, Helen Ross-Adams20, Li Chen12, Jucong Li13, Yingqia Hong13, Zsofia Kote-Jarai21, Xingang Cui22, Jianguo Hou23, Jianming Guo7, Lei Xu7, Changjun Yin5, Yuanping Zhou24, David E. Neal20, Tim Oliver1, Guangwen Cao2, Zhengdong Zhang3, Douglas F. Easton19, Claude Chelala1, The PRACTICAL Consortium, The CHIPGECS Group, Ali Amin Al Olama19, Rosalind A. Eeles21,25, Hongwei Zhang2, Yong-Jie Lu1
1Centre for Molecular Oncology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
2Department of Epidemiology, Second Military Medical University, Shanghai, 200433, China
3Department of Molecular and Genetic Toxicology, The Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, 210029, China
4Department of Urology, Wuxi Second People’s Hospital, Nanjing Medical University, Wuxi, 214002, China
5Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
6Department of Urology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
7Department of Urology, Zhongshan Hospital, Fudan University Medical College, Shanghai, 200032, China
8Liaoning People’s Hospital and Center of Experiment and Technology, China Medical University, Shenyang, 110001, China
9Program for Personalized Cancer Care, North Shore University Health System, Evanston, IL 60201, U.S.A
10Fudan Institute of Urology, Huashang Hospital, Fudan University, Shanghai, 200040, China
11Department of Urology, Tongji Hospital, Huazhong Science and Technology University, Wuhan, 430030, China
12Department of Urology, Xiehe Hospital, Huazhong Science and Technology University, Wuhan, 430022, China
13Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
14Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College, Hangzhou, 310009, China
15Department of Pathology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China
16Department of Urology, First Affiliated Hospital, Medical College, Zhengzhou University, Zhengzhou, 450003, China
17Department of Urology, North Sichuan Medical College, Nanchong, 637000, China
18Department of Nutrition Science, Shenyang Medical College, Shenyang, 110034, China
19Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge–Strangeways Research Laboratory, Cambridge, CB1 8RN, UK
20Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK
21Division of Genetics and Epidemiology, The Institute of Cancer Research, London, SM2 5NG, UK
22Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China
23Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai, 200433, China
24Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
25The Royal Marsden NHS Foundation Trust, London and Surrey, SM2 5NG, UK
*These authors have contributed equally to this work
Correspondence to:
Yong-Jie Lu, e-mail: [email protected]
Hongwei Zhang, e-mail: [email protected]
Keywords: Chinese prostate cancer, genetic risk, single-nucleotide polymorphism, predisposition, population difference
Received: September 02, 2015 Accepted: January 23, 2016 Published: February 8, 2016
ABSTRACT
Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.
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