Prostate Cancer Risk Alleles are Associated with Prostate Cancer Volume and Prostate Size

Abstract

Purpose Genome-wide association studies have identified an increasing number of single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. Some of these same genetic variants are also associated with serum PSA levels and lower urinary tract symptoms, raising the question whether the SNPs are truly biomarkers for prostate cancer or simply lead to detection bias. We therefore sought to determine whether the prostate cancer risk SNPs are more strongly associated with tumor volume or prostate volume. Materials and Methods The genotypes of 38 validated prostate cancer risk SNPs were determined in 1,321 Caucasian men who underwent radical prostatectomy. Univariate and multivariate analyses were performed to compare the relationship between SNP frequency, total prostate volume and tumor volume. Results On multivariate analysis, 2 SNPs on chromosome 8q24, rs16901979 (A) (p=0.01) and rs6983267 (G) (p=0.02), were significantly associated with increased tumor volume. In contrast, rs17632542 (T) (p=0.02), near the PSA gene on 19q13, was associated with significantly lower tumor volume, and rs10788160 (A) (p=0.01) on 10q26 was associated with a significantly larger prostate volume. Conclusions Analyses of 38 prostate cancer risk SNPs demonstrates a significant association between several SNPs on chromosome 8q24 and increased tumor volume but not prostate volume, suggesting they are bona fide markers for prostate cancer susceptibility and possibly more aggressive disease. Meanwhile, other “prostate cancer risk SNPs” are associated with PSA levels and either increased prostate volume or decreased tumor volume, suggesting a detection bias due to their phenotypic influence.

Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma

“…These genomic aberrations result in altered mRNA expression levels in tumour versus normal tissues (Figure 3(b)). Additionally, three of these genes ( MYC, KLF10 and PTK2 ) are located in a region of genomic instability on chromosome 8, which is associated with poor prognosis [37–39]. A detailed analysis of the chromosomal loci 8q, 10q and 14q, which harbour these genes, confirmed the presence of gross CN aberrations in both PC3 cells and L‐EVs (Figure 3(c)).…”

Risk Stratification of Prostate Cancer Using the Combination of Histogram Analysis of Apparent Diffusion Coefficient Across Tumor Diffusion Volume and Clinical Information: A Pilot Study

“…Given that MRI can visualize anatomical structure better than ultrasound, MRI‐based measurements of prostate volume and the derived PSA density were more accurate in our study compared with ultrasound‐based measurements. Reinhardt et al reported that tumor volume exhibited an association with genetic risk of PCa . In our study, all this information was included in risk modeling.…”

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

“…Previous studies have identified associations between SNPs within or near the PSA gene ( KLK3 ) and high-grade tumors and adverse clinical outcomes (Bensen et al 2013; Cramer et al 2008; Gudmundsson et al 2010; Lindstrom et al 2011; Reinhardt et al 2013; Slager et al 2003; Xu et al 2008). For example, using cohorts of European and Ashkenazi Jewish ancestry, two studies found that SNP rs2735839 in KLK3 was associated with PC-specific mortality (Gallagher et al 2010; Pomerantz et al 2011).…”