No Association Between a Polymorphic Variant of the Irs-1 Gene and Prostate Cancer Risk
Stark, J. R.
Mucci, L. A.
Febbo, P. G.
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CitationFall, K., J.R. Stark, L.A. Mucci, J. Chan, M.J. Stampfer, T. Kurth, P.G. Febbo, P. Kantoff, and J. Ma. 2008. “No Association between a Polymorphic Variant of the IRS-1 Gene and Prostate Cancer Risk.” The Prostate 68 (13): 1416–20. https://doi.org/10.1002/pros.20797.
AbstractOBJECTIVE. 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 1.195% 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. CONCLUSION S. Our data do not support an association between carriage of the variant IRS-1 gene and prostate cancer risk.
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