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Genome-wide association study identified novel genetic variant on SLC45A3 gene associated with serum levels prostate-specific antigen (PSA) in a Chinese population |
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| Authors: | Jielin Sun Sha Tao Yong Gao Tao Peng Aihua Tan Haiying Zhang Xiaobo Yang Xue Qin Yanling Hu Junjie Feng Seong-Tae Kim Xiaoling Lin Yongming Wu Ju Zhang Zhixian Li Li Li Linjian Mo Zhengjia Liang Deyi Shi Zhang Huang Xianghua Huang Ming Liu Qian Liu Shijun Zhang S. Lilly Zheng Jianfeng Xu Zengnan Mo |
| Affiliation: | 1. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA 2. Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China 3. Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China 4. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 5. Laboratory of Genomic Diversity, National Cancer Institute, NIH, Frederick, MD, USA 6. Department of Occupational Health and Environmental Health, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China 7. Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 8. Medical Scientific Research Center, Guangxi Medical University, Nanning, Guangxi, China 9. School of Life Sciences, Fudan-VARI Center for Genetic Epidemiology, Fudan University, Shanghai, China 10. State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai University, Tianjin, China 11. Medical Examination Center, Fangchenggang First People’s Hospital, Fangchenggang, Guangxi, China 12. Medical Examination Center, Guigang People’s Hospital, Guigang, Guangxi, China 13. Medical Examination Center, Yulin First People’s Hospital, Yulin, Guangxi, China 14. Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China 15. Fudan University Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China |
| Abstract: | Prostate-specific antigen (PSA) is a commonly used cancer biomarker for prostate cancer, and is often included as part of routine physical examinations in China. Serum levels of PSA may be influenced by genetic factors as well as other factors. A genome-wide association study (GWAS) conducted in a European population successfully identified six genetic loci that were significantly associated with PSA level. In this study, we aimed to identify common genetic variants that are associated with serum level of PSA in a Chinese population. We also evaluated the effects of those variants by creating personalized PSA cutoff values. A two-stage GWAS of PSA level was performed among men age 20–69 years and self-reported cancer-free participants that underwent routine physical examinations at several hospitals in Guangxi Province, China. Single nucleotide polymorphisms (SNPs) significantly associated with PSA levels in the first stage of sample (N = 1,999) were confirmed in the second stage of sample (N = 1,496). Multivariate linear regression was used to assess the independent contribution of confirmed SNPs and known covariates, such as age, to the level of PSA. SNPs in three regions were significantly associated with levels of PSA in this two-stage GWAS, and had combined P values between 4.62 × 10?17 and 6.45 × 10?37. The three regions are located on 1q32.1 at SLC45A3, 10q11.23 at MSMB, and 19q13.33 at KLK3. The region 1q32.1 at SLC45A3 was identified as a novel locus. Genetic variants contributed significantly more to the variance of PSA level than known covariates such as age. Personalized cutoff values of serum PSA, calculated based on the inheritance of these associated SNPs, differ considerably among individuals. Identification of these genetic markers provides new insight into the molecular mechanisms of PSA. Taking individual variation into account, these genetic variants may improve the performance of PSA to predict prostate cancer. |
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