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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Acknowledgments
We thank the local research teams from Fangchenggang First People’s Hospital, Guigang People’s Hospital and Yulin First People’s Hospital for their contribution to the recruitment of study subjects. We thank X-W Zou, H–C Zheng and O Li at the Genergy Biotechnology (Shanghai) Co., Ltd, for their assistance in the genotyping. Finally, we thank all study subjects for participating in the study. This work was partially supported by the General Program of National Natural Science Foundation of China (30945204, 30360124, 30260110), the Guangxi Provincial Department of Finance and Education (2009GJCJ150), and intramural funding from Fudan-VARI Center for genetic Epidemiology and intramural funding from Fudan University Institute of Urology.
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J. Sun, S. Tao, Y. Gao and T. Peng contributed equally to this work.
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Sun, J., Tao, S., Gao, Y. et al. Genome-wide association study identified novel genetic variant on SLC45A3 gene associated with serum levels prostate-specific antigen (PSA) in a Chinese population. Hum Genet 132, 423–429 (2013). https://doi.org/10.1007/s00439-012-1254-3
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DOI: https://doi.org/10.1007/s00439-012-1254-3