Pathological Aggressiveness of Prostatic Carcinomas Related to RNASEL R462Q Allelic Variants

Abstract

Purpose-Allelic variations in the HPC1/RNASEL gene, especially the R462Q single nucleotide polymorphism, have been associated with increased susceptibility to prostate cancer. Prior studies have suggested that HPC1-or R462Q-associated tumors present with more aggressive clinical features. We assessed a series of men undergoing radical prostatectomy for clinical and pathological measures of tumor aggressiveness according to the RNASEL R462Q genotype.Methods-A prospective analysis of 232 men treated for prostate cancer by radical prostatectomy was performed. Disease aggressiveness at time of diagnosis was assessed by age of disease onset, biopsy Gleason score, clinical T stage, and pretreatment PSA level. Tumor aggressiveness was assessed pathologically by tumor volume, extraprostatic extension, seminal vesicle involvement, and lymph node metastases. Clinical and pathological characteristics were then correlated with RNASEL genotype.Results-Of the 232 men studied, 104 (45%) were homozygous wild-type (RR), 101 (43%) were heterozygous (RQ), and 27 (12%) were homozygous for the R462Q variant (QQ), mirroring the distribution seen in the general population. No significant differences were seen between genotypes in age of disease onset, pretreatment characteristics or in pathologic features as assessed by surgical grade and pathological stage. QQ tumors were of smaller volume than other genotypes (p=0.02).Conclusions-This prospective study suggests that prostate cancer in patients with the R462Q allelic variant of the HPC1/RNASEL gene are not associated with more aggressive clinical or pathological features in radical prostatectomy specimens.

Association of HPC2/ELAC2 and RNASEL non‐synonymous variants with prostate cancer risk in African American familial and sporadic cases

“…Initially, Casey et al, (2002) showed that the R462Q variant resulted in a significant decrease in RNASEL enzymatic activity and that the variant was significantly associated with an increasing risk of prostate cancer in a case control cohort. Several subsequent studies have been reported, which suggest that RNASEL common variants are associated with risk of familial prostate cancer (17,35,36); however these findings are not universally replicable (37–41). Results of a meta-analysis of ten independent RNASEL genotyping studies for the variants E265X, R462Q, and D541E suggested that although there was no overall effect on prostate cancer risk, there was an ethnic associated increase in risk of prostate cancer (<2.0) with the D541E variant in Caucasians regardless of family history (42).…”

The role of BRCA1 and BRCA2 in prostate cancer

“…[25][26][27] While the clinical implications of common genetic variants associated with PCa risk remain unclear, [28][29][30][31][32][33][34] deleterious germline mutations in both genes, BRCA1 and BRCA2, have been associated with more aggressive disease and poor clinical outcomes.…”

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

“…22–24 These studies have either found no association, examined SNPs no longer considered PC-risk specific alleles or examined different SNPs from those in this analysis. To our knowledge, the present study is the first to include such a large number of PC-risk SNPs and their association to tumor volume and prostate size.…”