title: Genome-wide association study identified novel genetic variant on SLC45A3 gene associated with serum levels prostate-specific antigen (PSA) in a Chinese population.
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.
authors.affiliation: Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.forename: Yanling
authors.initials: Y
authors.lastname: Hu
authors.forename: Junjie
authors.initials: J
authors.lastname: Feng
authors.forename: Seong-Tae
authors.initials: ST
authors.lastname: Kim
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Lin
authors.forename: Yongming
authors.initials: Y
authors.lastname: Wu
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Linjian
authors.initials: L
authors.lastname: Mo
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Liang
authors.forename: Deyi
authors.initials: D
authors.lastname: Shi
authors.forename: Zhang
authors.initials: Z
authors.lastname: Huang
authors.forename: Xianghua
authors.initials: X
authors.lastname: Huang
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Lilly Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D002681:China; D002877:Chromosomes, Human / Q000235:genetics* / Q000378:metabolism; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D007610:Kallikreins / Q000097:blood*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; D009004:Monosaccharide Transport Proteins; C551031:SLC45a3 protein, human; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen