Prostate cancer risk and IRS1, IRS2, IGF1, and INS polymorphisms: strong association of IRS1 G972R variant and cancer risk.
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.
Neuhausen
Susan L
SL
Department of Medicine, Division of Epidemiology, University of California Irvine, Irvine, CA 92697-7550, USA. sneuhaus@uci.edu
Slattery
Martha L
ML
Garner
Chad P
CP
Ding
Yuan C
YC
Hoffman
Michael
M
Brothman
Arthur R
AR
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D006801:Humans; D007328:Insulin / Q000235:genetics*; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I