Relation of serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 to risk of prostate cancer (United States).
OBJECTIVE
Insulin-like growth factor I (IGF-I) exerts potent mitogenic and antiapoptotic effects on prostatic epithelial cells. Insulin-like growth factor binding protein-3 (IGFBP-3) modulates the effects of IGF-I, and independently induces apoptosis and inhibits cell growth. Previous studies have inconsistently associated IGF-I and IGFBP-3 with prostate cancer. To try and further clarify these potential associations, we undertook a sibling-matched case-control study.


METHODS
Serum IGF-I and IGFBP-3 were determined for 845 men (408 cases and 437 sibling controls). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the serum IGF levels and prostate cancer.


RESULTS
Among all study subjects, only the molar ratio of IGF-I to IGFBP-3 was associated with prostate cancer: comparing those in the highest to lowest quartiles gave an OR = 1.62 (95% CI = 1.02-2.57, trend-p = 0.04). Among men with clinically less aggressive disease, we observed positive associations between prostate cancer and high levels of IGF-I (OR = 2.78, 95% CI = 1.06-6.80, trend-p = 0.03), and IGFBP-3 (OR = 2.68, 95% CI = 1.08-6.80, trend-p = 0.04). Simultaneously modeling both left the IGF-I result essentially unchanged, while substantially weakening the IGFBP-3 association.


CONCLUSIONS
We found that a high IGF-I to IGFBP-3 molar ratio was associated with an increased risk of prostate cancer. Furthermore, high IGF-I was associated with increased risk of prostate cancer among men with less advanced disease at diagnosis. These results lend support to the hypothesis that IGF-I, or the IGF-I to IGFBP-3 molar ratio, is an important risk factor for prostate cancer.
Li
Li
L
Department of Family Medicine, Case Western Reserve University, Cleveland, OH 44106-4945, USA.
Yu
Herbert
H
Schumacher
Fredrick
F
Casey
Graham
G
Witte
John S
JS
D000368:Aged; D016022:Case-Control Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000209:etiology*; D012307:Risk Factors; D014481:United States
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I