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Known susceptibility SNPs for sporadic prostate cancer show a similar association with “hereditary” prostate cancer
Author(s) -
Cremers Ruben G.,
Galesloot Tessel E.,
Aben Katja K.,
van Oort Inge M.,
Vasen Hans F.,
Vermeulen Sita H.,
Kiemeney Lambertus A.
Publication year - 2015
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.22933
Subject(s) - single nucleotide polymorphism , logistic regression , receiver operating characteristic , prostate cancer , medicine , odds ratio , population , oncology , cancer , genome wide association study , penetrance , genetics , biology , genotype , environmental health , gene , phenotype
Background More than 70 single nucleotide polymorphisms (SNPs) have been reported to be associated with prostate cancer (PC) risk; these were mainly identified in the general population with predominantly sporadic PC (SPC). Previous studies have suggested similar associations between a selection of these SNPs and hereditary PC (HPC). Our aim was to evaluate the effect of all known PC risk SNPs and their discriminative value for SPC and HPC. Methods Seventy‐four PC susceptibility SNPs (reported in literature up to June 2014) were genotyped in a population‐based series of 620 SPC patients, 312 HPC patients from the national Dutch registry and 1819 population‐based referents. Association analyses were performed using logistic regression, focusing on directional consistency of the odds ratios (ORs) with those in the original reports, that is, whether the OR was in the same direction as in the original report. Discriminative performance was evaluated by a genetic risk score used in logistic regression and receiver operating characteristic (ROC) curve analyses. Results Directional consistency was seen for 62 SNPs in SPC and 64 SNPs in HPC, 56 of which overlapped. ORs were mostly higher for HPC with 22 ORs >1.25 versus 5 for SPC. Discriminative performance was better for HPC with an area under the ROC curve of 0.73 versus 0.64 for SPC. Conclusions A large overlap was found for the associations between low‐penetrance susceptibility SNPs and SPC and HPC, suggesting a similarity in genetic etiology. This warrants a reconsideration of “HPC” and a restrictive policy toward prostate‐specific antigen testing in men with a positive family history. Genetic risk scores might be used for PC risk stratification on the population level. Prostate 75: 474–483, 2015 © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.