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Prostate cancer risk and IRS1, IRS2, IGF1 , and INS polymorphisms: Strong association of IRS1 G972R variant and cancer risk
Author(s) -
Neuhausen Susan L.,
Slattery Martha L.,
Garner Chad P.,
Ding Yuan C.,
Hoffman Michael,
Brothman Arthur R.
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20216
Subject(s) - prostate cancer , medicine , oncology , cancer , prostate , irs1 , genotype , insulin , cancer research , insulin receptor , biology , insulin resistance , genetics , gene
BACKGROUND As cellular proliferation is central to the carcinogenic process, pathways that regulate proliferation may be important. Therefore, genes in the insulin and the insulin‐like growth factor signaling pathways are plausible candidates for susceptibility genes for prostate cancer. We hypothesized that functional polymorphisms in INS, IRS1, IRS2 , and IGF1 may be associated with prostate cancer. METHODS We studied 199 incident prostate cancer cases and 267 age‐matched controls. Genotyping was performed for the INS +1127 Ins‐PstI, IRS1 G972R, IRS2 G1079D, and the IGF1 CA‐repeat polymorphisms. Outcomes were prostate cancer, Gleason score, and AJCC stage. RESULTS The IRS1 G972R GR/RR genotypes were associated with a significant 2.8‐fold increased risk for prostate cancer (95% CI 1.5–5.1, P = 0.0007). The other variants were not significantly associated with prostate cancer. The IRS1 G972R GR/RR genotypes were also significantly associated with more advanced Gleason score ( P = 0.001) and AJCC stage ( P = 0.004). CONCLUSIONS These results support a role of the insulin and/or insulin‐like growth factor pathways in the etiology of prostate cancer. © 2005 Wiley‐Liss, Inc.