Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study.
BACKGROUND
Recent studies have suggested that men with elevated plasma levels of insulin-like growth factor-I (IGF-I) may have an increased risk of prostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I. In this study, we sought to determine the role of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiologic factors for prostate cancer.


METHODS
We conducted a nested case-control study within the Northern Sweden Health and Disease Cohort Study. We measured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samples from 149 men who had a diagnosis of prostate cancer between 1 month and 10 years after blood collection and among 298 control men. All statistical tests are two-sided.


RESULTS
Case subjects had statistically significantly higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confidence interval [CI] = 218-240 ng/mL] versus 214 ng/mL [95% CI = 208-221 ng/mL]; P =.02) and IGFBP-3 (2611 ng/mL [95% CI = 2518-2704 ng/mL] versus 2498 ng/mL [95% CI = 2437-2560 ng/mL]; P =.04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IGF-I (P:(for trend) =.02) and IGFBP-3 (P(for trend) =.03). In case subjects younger than 59 years at the time of blood collection, the risk associated with increased IGF-I was higher (P:(for trend) =.01), whereas the risk associated with increased IGFBP-3 was lower (P(for trend) =.44) than the corresponding risks in the full cohort. Prostate cancer risk was not associated with levels of IGFBP-1, IGFBP-2, or insulin.


CONCLUSIONS
Prostate cancer risk is increased in men with elevated plasma IGF-I. This association was particularly strong in younger men in this study, suggesting that circulating IGF-I may be specifically involved in the early pathogenesis of prostate cancer.
Stattin
P
P
Department of Urology and Andrology, Umeå University Hospital, Sweden. par.stattin@urologi.umu.se
Bylund
A
A
Rinaldi
S
S
Biessy
C
C
Déchaud
H
H
Stenman
U H
UH
Egevad
L
L
Riboli
E
E
Hallmans
G
G
Kaaks
R
R
D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood* / Q000276:immunology; D012306:Risk; D012307:Risk Factors; D013997:Time Factors
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D017430:Prostate-Specific Antigen