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No association between a polymorphic variant of the IRS-1 gene and prostate cancer risk
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- Fall, Katja, 1971- (author)
- Karolinska Institutet
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- Stark, J. R. (author)
- 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
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- Mucci, L. A. (author)
- 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
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- (creator_code:org_t)
- Hoboken, USA : John Wiley & Sons, 2008
- 2008
- English.
- In: The Prostate. - Hoboken, USA : John Wiley & Sons. - 0270-4137 .- 1097-0045. ; 68:13, s. 1416-20
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- Chan, J.
- Stampfer, M. J.
- Kurth, T.
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- Febbo, P. G.
- Kantoff, P.
- Ma, J.
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- MEDICAL AND HEALTH SCIENCES
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- The Prostate
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- Örebro University
- Karolinska Institutet
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