Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era.
OBJECTIVE
The insulin-like growth factor (IGF) axis is thought to contribute to the growth and progression of prostate cancer. Some prospective studies support a direct association between IGF-1 and prostate cancer, in particular advanced disease, whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the major IGF-1 binding protein in circulation. We prospectively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era.


METHODS
We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993, but before January 1998 among men in the Health Professionals Follow-up Study. Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer.


RESULTS
Men with higher concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92-2.03, p-trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07-2.46, p-trend=0.08) had a higher risk of prostate cancer. After mutual statistical adjustment, these associations were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69-1.99, p-trend=0.29) and IGFBP-3 (OR=1.40, 95% CI 0.80-2.44, p-trend=0.56). We found no significant association of IGF-1 with regionally invasive or metastatic (>/=T3b, N1, or M1) prostate cancer, although the number of these cases was small (n=42).


CONCLUSIONS
Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies, albeit weaker in magnitude. Our suggestive positive findings for IGFBP-3 are similar to some studies, but in direct contrast to others.
Platz
Elizabeth A
EA
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; and the Brady Urological Institute and the Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, USA. eplatz@jhsph.edu
Pollak
Michael N
MN
Leitzmann
Michael F
MF
Stampfer
Meir J
MJ
Willett
Walter C
WC
Giovannucci
Edward
E
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000473:pathology*; D012307:Risk Factors; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017430:Prostate-Specific Antigen