Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The RNASEL gene (2',5'-oligoisoadenylate-synthetase dependent) encodes a ribonuclease that mediates the antiviral and apoptotic activities of interferons. The RNASEL gene maps to the hereditary-prostate-cancer (HPC)-predisposition locus at 1q24-q25 (HPC1) and was recently shown to harbor truncating mutations in two families with linkage to HPC1. Here, we screened for RNASEL germline mutations in 66 Finnish patients with HPC, and we determined the frequency of the changes in the index patients from 116 families with HPC, in 492 patients with unselected prostate cancer (PRCA), in 223 patients with benign prostatic hyperplasia (BPH), and in 566 controls. A truncating mutation, E265X, was found in 5 (4.3%) of the 116 patients from families with HPC. This was significantly higher (odds ratio [OR] =4.56; P=.04) than the frequency of E265X in controls (1.8%). The highest mutation frequency (9.5%) was found in patients from families with four or more affected members. Possible segregation was detected only in a single family. However, the median age at disease onset for E265X carriers was 11 years less than that for noncarriers in the same families. In addition, of the four missense variants found, R462Q showed an association with HPC (OR=1.96; P=.07). None of the variants showed any differences between controls and either patients with BPH or patients with PRCA. We conclude that, although RNASEL mutations do not explain disease segregation in Finnish families with HPC, the variants are enriched in families with HPC that include more than two affected members and may also be associated with the age at disease onset. This suggests a possible modifying role in cancer predisposition. The impact that the RNASEL sequence variants have on PRCA burden at the population level seems small but deserves further study.
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PMID:Germline alterations of the RNASEL gene, a candidate HPC1 gene at 1q25, in patients and families with prostate cancer. 1194 39

The RNASEL gene (2', 5'-oligoisoadenylate synthetase-dependent) encodes a ribonuclease that plays a significant role in the apoptotic and antiviral activities of interferons. Various studies have used polymorphisms in the RNASEL gene to evaluate prostate cancer risk but studies that show an association between RNASEL Arg462Gln (1385G>A, R462Q, rs486907) polymorphism and prostate cancer risk are somewhat inconclusive. To assess the impact of RNASEL Arg462Gln polymorphism on prostate cancer risk, we conducted a meta-analysis of all available studies including 11,522 patients and 10,976 control subjects. The overall results indicated no positive association between the variant and prostate cancer risk. However, in a subgroup analysis by ethnicity, obvious associations were observed in Hispanic Caucasians for allelic contrast (OR = 1.18, 95% CI = 1.00 - 1.39, Pheterogeneity = 0.010), homozygote comparison (OR = 1.50, 95% CI = 1.02 - 2.20, Pheterogeneity = 0.001), and the recessive genetic model (OR = 1.44, 95% CI = 1.01 - 2.05, Pheterogeneity = 0.002) ; and in African descendants for homozygote comparison (OR = 2.59, 95% CI = 1.29 - 5.19, Pheterogeneity = 0.194) and the recessive genetic model (OR = 2.61, 95% CI = 1.30 - 5.23, Pheterogeneity = 0.195). In conclusion, the RNASEL Arg462Gln polymorphism may contribute to the risk of developing prostate cancer in African descendants and Hispanic Caucasians. Further larger and well-designed studies are warranted to evaluate this association in detail.
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PMID:Association of a common genetic variant in RNASEL and prostate cancer susceptibility. 2908 52