Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer.


9.5 times the risk of advanced-stage prostate cancer among men with low blood levels of a protein that binds and inactivates IGF-1.

TitleInsulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer.
Publication TypeJournal Article
Year of Publication2002
AuthorsChan JM, Stampfer MJ, Ma J, Gann P, Gaziano MJ, Pollak M, Giovannucci E
JournalJournal of the National Cancer Institute
Date Published2002 Jul 17
KeywordsAdult, Aged, Aged, 80 and over, Case-Control Studies, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Logistic Models, Male, Middle Aged, Prostatic Neoplasms, Risk, Sensitivity and Specificity

BACKGROUND: Plasma levels of insulin-like growth factor-I (IGF-I) have been associated with the risk of prostate cancer. However, the association of IGF-I with specific tumor stage and grade at diagnosis, which correlate with risk of recurrence and mortality, has not been studied rigorously. To determine whether plasma levels of IGF-I and its main circulating binding protein, IGF binding protein-3 (IGFBP-3), predict more aggressive forms of prostate cancer, we investigated the association between plasma levels of each and specific stages and grades of prostate cancer.

METHODS: We examined 530 case patients and 534 control subjects in a nested case-control study in the prospective Physicians' Health Study. Patients with prostate cancer diagnosed from 1982 through 1995 were matched to control subjects by age and smoking status. IGF-I and IGFBP-3 were measured in prospectively collected plasma samples. Conditional logistic regression models were used to estimate the relative risks (RRs) for prostate cancer associated with IGF-I and IGFBP-3, stratified on grade (Gleason score > or = 7 versus <7) and stage (early = stage A or B prostate cancer versus advanced = stage C or D prostate cancer). All statistical tests were two-sided.

RESULTS: Plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer (RR = 5.1, 95% confidence interval [CI] = 2.0 to 13.2 for highest versus lowest quartiles of IGF-I; RR = 0.2, 95% CI = 0.1 to 0.6 for highest versus lowest quartiles of IGFBP-3) but not of early-stage prostate cancer. Neither was differentially associated with Gleason score. Men with high IGF-I levels and low IGFBP-3 levels had an RR for advanced-stage prostate cancer of 9.5 (95% CI = 1.9 to 48.4) compared with men with low levels of both. Combining IGF-I and IGFPB-3 measurements with a standard prostate-specific antigen (PSA) measurement for prostate cancer screening increased the specificity (from 91% to 93%) but decreased sensitivity (from 40% to 36%) compared with measurement of PSA alone.

CONCLUSIONS: Circulating levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer, but their utility for screening patients with incident prostate cancer may be limited.

Alternate JournalJ. Natl. Cancer Inst.
PubMed ID12122101
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