RNASEL Gene Polymorphisms and the Risk of Prostate Cancer: a Meta-analysis

Abstract

Purpose: Studies revealing conflicting results on the role of RNASEL polymorphisms Glu265X, Arg462Gln, and Asp541Glu on prostate cancer risk led us to perform a meta-analysis to investigate the association of these polymorphisms and prostate cancer risk. Experimental Design: Relevant studies were selected by searching PubMed from January 1996 to August 2005 using keywords ''RNASEL gene AND prostate cancer.'' For each study, odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the gene effect. Pooled estimates of the OR were computed using the random effects model. Results: Ten studies were included in the meta-analysis. The overall results suggested no major influence of these variants on prostate cancer risk. However, analysis of the Asp541Glu polymorphism by ethnic populations showed that Asp/Glu (familial cases versus control: OR, 1.38; 95% CI, 1.04-1.82; sporadic cases versus control: OR, 1.26; 95% CI, 1.07-1.48; prostate cancer versus control: OR, 1.29; 95% CI, 1.12-1.48) and Asp/Glu + Glu/Glu (familial cases versus control: OR, 1.37; 95% CI, 1.10-1.70; sporadic cases versus control: OR, 1.24; 95% CI, 1.07-1.44; prostate cancer versus control: OR, 1.27; 95% CI, 1.13-1.44) increased prostate cancer risk in Caucasians, thus suggesting a dominant model for the Glu variant. Conclusions: Compared with the genotype Asp/Asp, the Glu variant at the Asp541Glu polymorphism increases prostate cancer risk by <2-fold in Caucasians, regardless of family history of the disease. This suggests that genuine genetic effects of this polymorphism may account for only a part of prostate cancer in the Caucasian population.Prostate cancer is the most frequently occurring cancer among men in most developed countries. The rates are the highest in the United States, Canada, Sweden, Australia, and France (48.1-137.0 cases per 100,000 person-years during [1988][1989][1990][1991][1992]; intermediate in European countries (23.9-31.0 cases per 100,000 person-years); and lowest in Asian countries (2.3-9.8 cases per 100,000 person-years; ref. 1). Various casecontrol and cohort studies investigating the role of family history as a risk factor for prostate cancer (2 -7) revealed increased risk of prostate cancer across different ethnicity. This supports the possibility of a common genetic basis for this disease (7).Significant linkage between prostate cancer and chromosome 1q24-25, now denoted as HPC1, has been reported (8 -10) and confirmed by the International Collaboration on Prostate Cancer Genetics, which pooled 772 families from nine international groups (11). One of the candidate genes within the HPC1 region is 2 ¶-5 ¶-oligoadenylate -dependent RNase L (RNASEL; MIM 601518 and 180435), which encodes a constitutively expressed latent endoribonuclease that mediates the antiviral and proapoptotic activities of the IFN-inducible 2-5A system. The linkage of HPC1 to RNASEL suggests that RNase L directly or indirectly suppresses one or more steps in prostate tumorigenesis and/or metastasis. The RNASEL gene ...

Evaluation of Cellular Determinants Required for In Vitro Xenotropic Murine Leukemia Virus-Related Virus Entry into Human Prostate Cancer and Noncancerous Cells

“…Indeed, several epidemiologic studies have supported the involvement of the RNASEL gene in the prostate cancer etiology (4,5,30,31), whereas other studies do not (9,22,34,43). Some studies have reported that individuals with a single mutated copy of the RNASEL gene have a 50% increased risk for prostate cancer, whereas those with homozygous mutant RNASEL alleles have a 2-fold-increased risk of prostate cancer (5).The RNASEL gene encodes for the RNase L protein, a constitutively expressed latent endoribonuclease, which mediates the interferon-inducible 2-5A system against viral and/or cellular double-stranded RNAs (8,16,20,23,49,50). The RNase L "Q" variant allele (R462Q) shows a 3-fold decrease in catalytic activity compared to the wild-type enzyme (5, 44).…”

“…The RNASEL gene encodes for the RNase L protein, a constitutively expressed latent endoribonuclease, which mediates the interferon-inducible 2-5A system against viral and/or cellular double-stranded RNAs (8,16,20,23,49,50). The RNase L "Q" variant allele (R462Q) shows a 3-fold decrease in catalytic activity compared to the wild-type enzyme (5, 44).…”

Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome After Radiation Therapy for Localized Prostate Cancer

“…We did not assess complete coverage of potential variation across the RNASEL gene. Although we chose to sequence three RNASEL SNPs based on previous study findings (16,19,(35)(36)(37), including two known missense mutations, the mechanism by which rs12757998 may act to increase circulating inflammatory mediators or impact radiation-response remains unknown, and this variant could potentially be a marker for the true causal variant. Also, although there were relatively few men who developed lethal prostate cancer, we cannot exclude the possibility that our inability to detect a statistically significant association between rs12757998 and lethal cancer was not the result of a differential biologic effect rather than a lack of power.…”

“…These SNPs were selected based on previously established functional significance (16,19,(35)(36)(37). Genotyping was performed in a blinded fashion after extraction of DNA from whole blood using a standard QIAmp kit (QIAGEN Inc. Chatsworth, CA) protocol using Biotrove Open Array SNP Genotyping Platform at the Harvard Medical School -Partners Healthcare Center for Genetics and Genomics.…”

R462Q Mutation in Prostate Cancer Specimens

“…The RNASEL is expressed by the RNASEL gene localized on the chromosome 1q24-25 (HPC-1), a region for hereditary prostate cancer (3). In some studies a significant relationship has been demonstrated between the chromosome 1q24-25 (HPC1) and prostate cancer risk (4). RNASEL, a role playing gene in regulating cell proliferation, apoptosis and tumor-suppressor cell, is one the candidate genes within the HPC1 region (5).…”