Document Detail


2'-5' oligoadenylate synthetase 1 polymorphism is associated with prostate cancer.
MedLine Citation:
PMID:  21638280     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The antiviral, proapoptotic, antiproliferative gene 2'-5' oligoadenylate synthetase (2-5OAS1) converts adenosine triphosphate into a series of 2'-5' oligoadenylates (2-5A). In turn, 2-5A activates latent ribonuclease (RNaseL), a candidate hereditary prostate cancer gene. OAS1 polymorphism (reference single nucleotide polymorphism [SNP] 2660 [rs2660]) has been associated with increased susceptibility to infections and various diseases. In general, the low-enzyme-activity adenine-adenine (AA) genotype promotes susceptibility, whereas the high-enzyme-activity guanosine-guanosine (GG) genotype confers protection. In this study, the authors investigated the association of this functional OAS1 polymorphism (rs2660) with prostate cancer.
METHODS: Sample size and power were calculated using a power calculation software program for case-control genetic association analyses. Genomic DNA samples from a control group (n = 140) and from a case group of patients with prostate cancer (n = 164) were used for genotyping SNPs rs2660, rs1131454, and rs34137742 in all samples. Statistical analyses were performed using a logistic regression model.
RESULTS: A significant association was observed between the rs2660 genotype (A/G) and prostate cancer. Genotype AA increased the risk, whereas genotype GG decreased the risk of prostate cancer. The GG genotype was not observed in the African American samples. The AA genotype also increased the risk of prostate cancer with age.
CONCLUSIONS: The OAS1 SNP rs2660 AA genotype was associated significantly with prostate cancer, whereas the GG genotype protected against prostate cancer. OAS1 rs2660 may be a prostate cancer susceptibility polymorphism, which is a significant observation, especially in a context of the OAS1-RNaseL pathway. Thus, a functional defect in OAS1 because of the rs2660 SNP not only can attenuate RNaseL function but also can alter cell growth and apoptosis independent of RNaseL.
Authors:
Sanjay Mandal; Fisseha Abebe; Jaideep Chaudhary
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2011-06-02
Journal Detail:
Title:  Cancer     Volume:  117     ISSN:  1097-0142     ISO Abbreviation:  Cancer     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-05     Completed Date:  2012-04-11     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5509-18     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American Cancer Society.
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MeSH Terms
Descriptor/Qualifier:
2',5'-Oligoadenylate Synthetase / genetics*,  metabolism
Case-Control Studies
Cell Line, Tumor
Genetic Predisposition to Disease
Genomics
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Prostatic Neoplasms / enzymology*,  genetics*
Retrospective Studies
Grant Support
ID/Acronym/Agency:
G12-RR03034/RR/NCRR NIH HHS; G12-RR03062/RR/NCRR NIH HHS; P20 MD002285/MD/NIMHD NIH HHS; P20 MD002285-01/MD/NIMHD NIH HHS; P20MD002285-01/MD/NIMHD NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.7.-/2',5'-Oligoadenylate Synthetase; EC 2.7.7.-/OAS1 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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