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No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm; Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.ORCID iD: 0000-0002-3649-2639
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Department of Medicine, Brigham Women’s Hospital and Harvard Medical School, Boston, USA.
Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA.
Departments of Epidemiology & Biostatistics and Urology, University of California, San Francisco, USA.
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2008 (English)In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 68, no 13, p. 1416-20Article in journal (Refereed) Published
Abstract [en]

Objective: Insulin receptor substrate-1 (IRS-1) acts as a docking protein between the insulin-like growth factor-1 (IGF-1) receptor and intracellular signaling molecules in the IGF-1 signaling pathway. Accumulating data support a role of IGF-1 in prostate carcinogenesis. We assessed the influence of the most common IRS-1 gene polymorphism (Gly972Arg) on prostate cancer risk, alone and in combination with IGF-1 and other components in the IGF-1 signaling pathway.

Materials and methods: In a nested case-control study within the Physicians' Health Study, the IRS-1 polymorphism was assayed from prospectively collected samples from 564 incident prostate cancer cases and 758 controls matched on age and smoking. We calculated relative risks (RR) and 95% confidence intervals (CI) using conditional logistic regression.

Results: Among the controls, 0.8% were homozygous (AA) and 12% were heterozygous (GA) for the polymorphic allele. There was no association between carriage of the A allele and total prostate cancer risk (RR = 1.1 95% CI = 0.8-1.5), advanced disease (stage C or D or lethal prostate cancer, RR = 1.3 95% CI = 0.8-2.3), or plasma IGF-1 levels. We explored possible interactions with body mass index and components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN but none of these factors influenced the relation between IRS-1 genotype and prostate cancer risk.

Conclusions: Our data do not support an association between carriage of the variant IRS-1 gene and prostate cancer risk.

Place, publisher, year, edition, pages
Hoboken, USA: John Wiley & Sons, 2008. Vol. 68, no 13, p. 1416-20
National Category
Medical and Health Sciences Cancer and Oncology
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URN: urn:nbn:se:oru:diva-41463DOI: 10.1002/pros.20797ISI: 000258912500006PubMedID: 18615538Scopus ID: 2-s2.0-50949096832OAI: oai:DiVA.org:oru-41463DiVA, id: diva2:811693
Available from: 2015-05-12 Created: 2015-01-14 Last updated: 2017-12-04Bibliographically approved

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