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Abstract

Volume 15, Issue 3 (May 2013) 15, 314–322; 10.1038/aja.2013.42

Prostate cancer risk-associated genetic markers and their potential clinical utility

Jianfeng Xu1,2,3,4, Jielin Sun4 and S Lilly Zheng4

1 Fudan Institute of Urology, Huashan Hospital, Fudan UniversityFudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China
2 State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China
3 Center for Genetic Epidemiology, School of Life Sciences, Fudan University, Shanghai 200433, China
4 Center for Cancer Genomics, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA

Correspondence: Dr J Xu (jxu8088@gmail.com)

Received 28 February 2013; Revised 16 March 2013; Accepted 18 March 2013 Advance online publication 8 April 2013

Abstract

Prostate cancer (PCa) is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and low-penetrance PCa risk-associated single-nucleotide polymorphisms (SNPs) from genetic association studies in PCa cases and controls, especially those from genome-wide association studies (GWASs). A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations.


Keywords:biopsy; Chinese; family history; genetic score; heritability; prostate cancer (PCa); prostate-specific antigen (PSA); PSA screen; single-nucleotide polymorphisms (SNPs)

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