New variants at 10q26 and 15q21 are associated with aggressive prostate cancer in a genome-wide association study from a prostate biopsy screening cohort

Abstract

; Toronto ON Canada Purpose: To identify and examine polymorphisms of genes associated with aggressive and clinical significant forms of prostate cancer among a screening cohort.Experimental Design: We conducted a genome-wide association study among patients with aggressive forms of prostate cancer and biopsy-proven normal controls ascertained from a prostate cancer screening program. We then examined significant associations of specific polymorphisms among a prostate cancer screened cohort to examine their predictive ability in detecting prostate cancer.Results: We found significant associations between aggressive prostate cancer and five single nucleotide polymorphisms (SNPs) in the 10q26 (rs10788165, rs10749408, and rs10788165, p value for association 1.3 ¾ 10 210 to 3.2 ¾ 10 211 ) and 15q21 (rs4775302 and rs1994198, p values for association 3.1 ¾ 10 28 to 8.2 ¾ 10 29 ) regions. Results of a replication study done in 3439 patients undergoing a prostate biopsy, revealed certain combinations of these SNPs to be significantly associated not only with prostate cancer but with aggressive forms of prostate cancer using an established classification criterion for prostate cancer progression (odds ratios for intermediate to high-risk disease 1.8-3.0, p value 0.003-0.001). These SNP combinations were also important clinical predictors for prostate cancer detection based on nomogram analysis that assesses prostate cancer risk.Conclusions: Five SNPs were found to be associated with aggressive forms of prostate cancer. We demonstrated potential clinical applications of these associations.

Genetic Variation in Prostate-Specific Antigen–Detected Prostate Cancer and the Effect of Control Selection on Genetic Association Studies

“…Our analysis suggests that rs10788160-A is associated with higher PSA levels, whilst rs10788160-G is associated with lower levels. A previous study reported a positive association between rs11199874-G and PrCa (25). This association could be driven by the large proportion (>50%) of high PSA (4-10 ng/ml) controls used rather than reflecting a true association because this high PSA enriched control sample is likely to have a higher proportion of individuals with the allele rs11199874-A; this could in turn account for the positive association of PrCa with rs11199874-G (the opposite allele to rs11199874-A).…”

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

“…A meta-analysis aimed at determining whether genetic variants were associated with adverse pathology features reported that SNP rs11672691 showed associations with more aggressive tumors (Amin Al Olama et al 2013). Additionally, results from other GWAS and linkage analyses have reported risk loci associated with aggressive disease amongst familial cases (Casey et al 2006; Chang et al 2005; Gudmundsson et al 2008; Kirkland et al 2010; Liu et al 2011; Nam et al 2011; Nurminen et al 2011; Schaid et al 2006; Schaid et al 2007; Slager et al 2006; Stanford et al 2006; Witte et al 2000). In addition, Shui et al reported that 8 SNPs were associated with lethal PC (Shui et al 2014).…”

Coexpression and expression quantitative trait loci analyses of the angiogenesis gene-gene interaction network in prostate cancer

“…Angiogenesis involves the division and migration of endothelial cells and leads to microvasculature formation (3,4). Based on the genome-wide association studies (GWAS), angiogenesis genetic variants or single nucleotide polymorphisms (SNPs) in or near IL-16 (rs4072111) and FGFR2 (rs11199874, rs10749408 and rs10788165) are significantly associated with PCa aggressiveness (5,6). In candidate gene studies, several angiogenesis SNPs are shown to be associated with PCa prognosis.…”