Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies

Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, Metter EJ, Chen C, Weiss NS, Fitzpatrick A, Hsing AW, Lacey JV, Jr., Helzlsouer K, Rinaldi S, Riboli E, Kaaks R, Janssen JA, Wildhagen MF, Schroder FH, Platz EA, Pollak M, Giovannucci E, Schaefer C, Quesenberry CP, Jr., Vogelman JH, Severi G, English DR, Giles GG, Stattin P, Hallmans G, Johansson M, Chan JM, Gann P, Oliver SE, Holly JM, Donovan J, Meyer F, Bairati I, Galan P (2008) Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med 149:461-471, W483-468

BACKGROUND: Some, but not all, published results have shown an association between circulating blood levels of some insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) and the subsequent risk for prostate cancer. PURPOSE: To assess the association between levels of IGFs and IGFBPs and the subsequent risk for prostate cancer. DATA SOURCES: Studies identified in PubMed, Web of Science, and CancerLit. STUDY SELECTION: The principal investigators of all studies that published data on circulating concentrations of sex steroids, IGFs, or IGFBPs and prostate cancer risk using prospectively collected blood samples were invited to collaborate. DATA EXTRACTION: Investigators provided individual participant data on circulating concentrations of IGF-I, IGF-II, IGFBP-II, and IGFBP-III and participant characteristics to a central data set in Oxford, United Kingdom. DATA SYNTHESIS: The study included data on 3700 men with prostate cancer and 5200 control participants. On average, case patients were 61.5 years of age at blood collection and received a diagnosis of prostate cancer 5 years after blood collection. The greater the serum IGF-I concentration, the greater the subsequent risk for prostate cancer (odds ratio [OR] in the highest vs. lowest quintile, 1.38 [95% CI, 1.19 to 1.60]; P < 0.001="" for="" trend).="" neither="" igf-ii="" nor="" igfbp-ii="" concentrations="" were="" associated="" with="" prostate="" cancer="" risk,="" but="" statistical="" power="" was="" limited.="" insulin-like="" growth="" factor="" i="" and="" igfbp-iii="" were="" correlated="" (r="0.58)," and="" although="" igfbp-iii="" concentration="" seemed="" to="" be="" associated="" with="" prostate="" cancer="" risk,="" this="" was="" secondary="" to="" its="" association="" with="" igf-i="" levels.="" insulin-like="" growth="" factor="" i="" concentrations="" seemed="" to="" be="" more="" positively="" associated="" with="" low-grade="" than="" high-grade="" disease;="" otherwise,="" the="" association="" between="" igfs="" and="" igfbps="" and="" prostate="" cancer="" risk="" had="" no="" statistically="" significant="" heterogeneity="" related="" to="" stage="" or="" grade="" of="" disease,="" time="" between="" blood="" collection="" and="" diagnosis,="" age="" and="" year="" of="" diagnosis,="" prostate-specific="" antigen="" level="" at="" recruitment,="" body="" mass="" index,="" smoking,="" or="" alcohol="" intake.="" limitations:="" insulin-like="" growth="" factor="" concentrations="" were="" measured="" in="" only="" 1="" sample="" for="" each="" participant,="" and="" the="" laboratory="" methods="" to="" measure="" igfs="" differed="" in="" each="" study.="" not="" all="" patients="" had="" disease="" stage="" or="" grade="" information,="" and="" the="" diagnosis="" of="" prostate="" cancer="" may="" differ="" among="" the="" studies.="" conclusion:="" high="" circulating="" igf-i="" concentrations="" are="" associated="" with="" a="" moderately="" increased="" risk="" for="" prostate="">