Inherited genetic markers discovered to date are able to identify a significant number of men at considerably elevated risk for prostate cancer.
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.
Sun
Jielin
J
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Kader
A Karim
AK
Hsu
Fang-Chi
FC
Kim
Seong-Tae
ST
Zhu
Yi
Y
Turner
Aubrey R
AR
Jin
Tao
T
Zhang
Zheng
Z
Adolfsson
Jan
J
Wiklund
Fredrik
F
Zheng
S Lilly
SL
Isaacs
William B
WB
Grönberg
Henrik
H
Xu
Jianfeng
J
D000368:Aged; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012306:Risk
D005819:Genetic Markers