Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin‐like growth factor I, insulin‐like growth factor binding protein 3, and insulin

Abstract

BACKGROUNDThere have been several epidemiologic studies investigating the association between circulating levels of insulin‐like growth factor I (IGF‐I), insulin‐like growth factor binding protein 3 (IGFBP‐3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case–control study within the Cardiovascular Health Study cohort.METHODSIn men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n = 174), the levels of IGF‐I, IGFBP‐3, and insulin were measured on blood samples that were obtained 1–9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age.RESULTSRelative to the men with IGF‐I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95% confidence interval [95% CI], 0.43–1.38), 0.73 (95% CI, 0.41–1.30), and 0.67 (95% CI, 0.37–1.25), respectively. The results were influenced little by adjustment for levels of IGFBP‐3 or, instead, by evaluating the molar IGF‐I/IGFBP‐3 ratio. An analysis that was restricted to men who had plasma prostate‐specific antigen levels < 4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP‐3 were 0.91 (95% CI, 0.49–1.68), 0.47 (95% CI, 0.25–0.94), and 0.65 (95% CI, 0.35–1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical.CONCLUSIONSThe IGF‐I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP‐3 level was associated with a modest decrease in risk. Cancer 2005. © 2004 American Cancer Society.

Insulin-like growth factors and cancer: no role in screening. Evidence from the BUPA study and meta-analysis of prospective epidemiological studies

“…Table 3 and Figure 1 shows the meta-analysis of IGF-1, IGF-2 and IGFBP-3 results from published prospective studies and the results from the present study (there were no published studies on IGF-2 and lung cancer). This analysis includes all the studies in the earlier analysis by Renehan et al (2004) together with eight others (Lacey et al, 2001;Wakai et al, 2002;Nomura et al, 2003;Woodson et al, 2003;Stattin et al, 2004;Chen et al, 2005;Meyer et al, 2005;Platz et al, 2005). The meta-analysis was restricted to data from prospective studies to minimise any effects of the cancer on the measurements made.…”

Recreational physical activity and risk of prostate cancer: A prospective population‐based study in Norway (the HUNT study)

“…24,25 Insulin appears to regulate the production and metabolism of testosterone, 26 whereas IGF-I stimulates proliferation and inhibits apoptosis in prostate cancer cells, and has been associated with increased prostate cancer risk in some, 19,27 but not all epidemiologic studies. 28,29 A recent cohort study from Sweden showed an almost threefold higher risk of advanced prostate cancer among men in the highest compared to the lowest quartile of IGF-I. 30 Another part of the IGF-axis, the IGF binding proteins (IGFBPs), are also influenced by physical activity 24,25 and it has been shown that IGFBP-3 stimulates apoptosis in human prostate cancer cells.…”

“…5,6 Nonetheless, the results of 2 recent cohort studies from the United States suggest that physical activity may be associated with reduced risk of advanced prostate cancer. 7,8 We have prospectively studied the association between recreational physical activity, measured as frequency, duration and intensity of exercise, and risk of prostate cancer in a cohort of 29,110 Norwegian men who participated in a population-based study between 1984 and 2003 (the HUNT study). This study represents an extension and update of analyses previously reported from a follow-up through 1996.…”

Obesity Biomarkers, Metabolism and Risk of Cancer: An Epidemiological Perspective

“…A meta-analysis including four prospective studies on IGF-1 and risk of ovarian cancer did not provide evidence for this pathway [32]. While epidemiologic evidence relating circulating insulin or C-peptide [33][34][35][36][37][38][39] to risk of prostate cancer is inconclusive, pre-diagnostic circulating IGF-1 concentrations have been consistently related to higher risk of prostate cancer, especially lowgrade tumors [40]. Prospective investigations on insulin/IGF-1 and risk of liver cancer are scarce, although higher pre-diagnostic concentrations of C-peptide have been related to higher risk of liver cancer in EPIC [41].…”