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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• 作者：Jielin Sun (1)
  Sha Tao (1)
  Yong Gao (2) (3)
  Tao Peng (4) (5)
  Aihua Tan (3)
  Haiying Zhang (3) (6)
  Xiaobo Yang (3) (6)
  Xue Qin (3) (7)
  Yanling Hu (3) (8)
  Junjie Feng (1)
  Seong-Tae Kim (1)
  Xiaoling Lin (9)
  Yongming Wu (2)
  Ju Zhang (10)
  Zhixian Li (3)
  Li Li (8)
  Linjian Mo (2)
  Zhengjia Liang (11)
  Deyi Shi (11)
  Zhang Huang (11)
  Xianghua Huang (12)
  Ming Liu (13)
  Qian Liu (14)
  Shijun Zhang (3)
  S. Lilly Zheng (1)
  Jianfeng Xu (1) (15) (9)
  Zengnan Mo (2) (3)
  
• 刊名：Human Genetics
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：132
• 期：4
• 页码：423-429
• 全文大小：284KB
• 参考文献：1. Bansal A, Murray DK, Wu JT, Stephenson RA, Middleton RG, Meikle AW (2000) Heritability of prostate-specific antigen and relationship with zonal prostate volumes in aging twins. J Clin Endocrinol Metab 85:1272-276 CrossRef
  2. Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, Field HI, Southey MC, Severi G, Donovan JL, Hamdy FC, Dearnaley DP, Muir KR, Smith C, Bagnato M, Ardern-Jones AT, Hall AL, O’Brien LT, Gehr-Swain BN, Wilkinson RA, Cox A, Lewis S, Brown PM, Jhavar SG, Tymrakiewicz M, Lophatananon A, Bryant SL, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Fisher C, Jamieson C, Cooper CS, English DR, Hopper JL, Neal DE, Easton DF (2008) Multiple newly identified loci associated with prostate cancer susceptibility. Nat Genet 40:316-21. doi:10.1038/ng.90 CrossRef
  3. Gudmundsson J, Besenbacher S, Sulem P, Gudbjartsson DF, Olafsson I, Arinbjarnarson S, Agnarsson BA, Benediktsdottir KR, Isaksson HJ, Kostic JP, Gudjonsson SA, Stacey SN, Gylfason A, Sigurdsson A, Holm H, Bjornsdottir US, Eyjolfsson GI, Navarrete S, Fuertes F, Garcia-Prats MD, Polo E, Checherita IA, Jinga M, Badea P, Aben KK, Schalken JA, van Oort IM, Sweep FC, Helfand BT, Davis M, Donovan JL, Hamdy FC, Kristjansson K, Gulcher JR, Masson G, Kong A, Catalona WJ, Mayordomo JI, Geirsson G, Einarsson GV, Barkardottir RB, Jonsson E, Jinga V, Mates D, Kiemeney LA, Neal DE, Thorsteinsdottir U, Rafnar T, Stefansson K (2010) Genetic correction of PSA values using sequence variants associated with PSA levels. Sci Transl Med 2: 62ra92. doi:10.1126/scitranslmed.3001513
  4. Hernandez J, Thompson IM (2004) Prostate-specific antigen: a review of the validation of the most commonly used cancer biomarker. Cancer 101:894-04. doi:10.1002/cncr.20480 CrossRef
  5. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69-0. doi:10.3322/caac.20107 CrossRef
  6. Jian L, Xie LP, Lee AH, Binns CW (2004) Protective effect of green tea against prostate cancer: a case-control study in southeast China. Int J Cancer 108:130-35. doi:10.1002/ijc.11550 CrossRef
  7. Marchini J, Howie B, Myers S, McVean G, Donnelly P (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39:906-13. doi:10.1038/ng2088 CrossRef
  8. Perner S, Rupp NJ, Braun M, Rubin MA, Moch H, Dietel M, Wernert N, Jung K, Stephan C, Kristiansen G (2012) Loss of SLC45A3 protein (prostein) expression in prostate cancer is associated with SLC45A3-ERG gene rearrangement and an unfavorable clinical course. Int J Cancer. doi:10.1002/ijc.27733
  9. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38:904-09. doi:10.1038/ng1847 CrossRef
  10. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81:559-75. doi:10.1086/519795 CrossRef
  11. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Maattanen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A (2009) Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320-328. doi:10.1056/NEJMoa0810084 CrossRef
  12. Shao Q, Ouyang J, Fan Y, Xie J, Zhou J, Wu J, Karim Kader A, Xu J, Liu G, Shan Y, Wen D, Zhang Y et al (2012) Prostate cancer in the senior men from rural areas in east district of China: contemporary management and 5-year outcomes at multi-institutional collaboration. Cancer Lett 315:170-77. doi:10.1016/j.canlet.2011.09.035 CrossRef
  13. Tan A, Gao Y, Yang X, Zhang H, Qin X, Mo L, Peng T, Xia N, Mo Z et al (2011) Low serum osteocalcin level is a potential marker for metabolic syndrome: results from a Chinese male population survey. Metab, Clin Exp 60:1186-192. doi:10.1016/j.metabol.2011.01.002 CrossRef
  14. Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, Parnes HL, Coltman CA Jr (2005) Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0?ng/ml or lower. JAMA 294:66-0. doi:10.1001/jama.294.1.66 CrossRef
  15. Walker MG, Volkmuth W, Sprinzak E, Hodgson D, Klingler T (1999) Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes. Genome Res 9:1198-203 CrossRef
  16. Xu J, Kalos M, Stolk JA, Zasloff EJ, Zhang X, Houghton RL, Filho AM, Nolasco M, Badaro R, Reed SG (2001) Identification and characterization of prostein, a novel prostate-specific protein. Cancer Res 61:1563-568
  17. Xu J, Mo Z, Ye D, Wang M, Liu F, Jin G, Xu C, Wang X, Shao Q, Chen Z, Tao Z, Qi J, Zhou F, Wang Z, Fu Y, He D, Wei Q, Guo J, Wu D, Gao X, Yuan J, Wang G, Xu Y, Yao H, Dong P, Jiao Y, Shen M, Yang J, Ou-Yang J, Jiang H, Zhu Y, Ren S, Zhang Z, Yin C, Dai B, Hu Z, Yang Y, Wu Q, Chen H, Peng P, Zheng Y, Zheng X, Xiang Y, Long J, Gong J, Na R, Lin X, Yu H, Tao S, Feng J, Sun J, Liu W, Hsing A, Rao J, Ding Q, Wiklund F, Gronberg H, Shu XO, Zheng W, Shen H, Jin L, Shi R, Lu D, Zhang X, Zheng SL, Sun Y (2012) Genome-wide association study in Chinese men identifies two new prostate cancer risk loci at 9q31.2 and 19q13.4. Nat Genet. doi:10.1038/ng.2424
  
• 作者单位：Jielin Sun (1)
  Sha Tao (1)
  Yong Gao (2) (3)
  Tao Peng (4) (5)
  Aihua Tan (3)
  Haiying Zhang (3) (6)
  Xiaobo Yang (3) (6)
  Xue Qin (3) (7)
  Yanling Hu (3) (8)
  Junjie Feng (1)
  Seong-Tae Kim (1)
  Xiaoling Lin (9)
  Yongming Wu (2)
  Ju Zhang (10)
  Zhixian Li (3)
  Li Li (8)
  Linjian Mo (2)
  Zhengjia Liang (11)
  Deyi Shi (11)
  Zhang Huang (11)
  Xianghua Huang (12)
  Ming Liu (13)
  Qian Liu (14)
  Shijun Zhang (3)
  S. Lilly Zheng (1)
  Jianfeng Xu (1) (15) (9)
  Zengnan Mo (2) (3)
  
  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
  
• ISSN：1432-1203

文摘

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 20-9?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?7 and 6.45 × 10?7. 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.