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Inherited genetic markers discovered to date are able to identify a significant number of men at considerably elevated risk for prostate cancer
Author(s) -
Sun Jielin,
Kader A. Karim,
Hsu FangChi,
Kim SeongTae,
Zhu Yi,
Turner Aubrey R.,
Jin Tao,
Zhang Zheng,
Adolfsson Jan,
Wiklund Fredrik,
Zheng S. Lilly,
Isaacs William B.,
Grönberg Henrik,
Xu Jianfeng
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21256
Subject(s) - single nucleotide polymorphism , prostate cancer , medicine , snp , population , family history , oncology , risk assessment , cancer , gynecology , genetics , biology , genotype , gene , environmental health , computer security , computer science
BACKGROUND Prostate cancer (PCa) risk‐associated single‐nucleotide polymorphisms (SNPs) are continuously being discovered. Their ability to identify men at high risk and the impact of increasing numbers of SNPs on predictive performance are not well understood. METHODS Absolute risk for PCa was estimated in a population‐based case–control study in Sweden (2,899 cases and 1,722 controls) using family history and three sets of sequentially discovered PCa risk‐associated SNPs. Their performance in predicting PCa was assessed by positive predictive values (PPV) and sensitivity. RESULTS SNPs and family history were able to differentiate individual risk for PCa and identify men at higher risk; ∼18% and ∼8% of men in the study had 20‐year (55–74 years) absolute risks that were twofold (0.24) or threefold (0.36) greater than the population median risk (0.12), respectively. When predictive performances were compared at absolute risk cutoffs of 0.12, 0.24, or 0.36, PPV increased considerably (∼20%, ∼30%, and ∼37%, respectively) while sensitivity decreased considerably (∼55%, ∼20%, and ∼10%, respectively). In contrast, when increasing numbers of SNPs (5, 11, and 28 SNPs) were used in risk prediction, PPV approached a constant value while sensitivity increased steadily. CONCLUSIONS SNPs discovered to date are suitable for risk prediction while additional SNPs discovered in the future may identify more subjects at higher risk. Men identified as high risk by SNP‐based testing may be targeted for PCa screening or chemoprevention. The clinical impact on improving the effectiveness of these interventions can be and should be assessed. Prostate 77:421–430, 2011. © 2010 Wiley‐Liss, Inc.