Insulin-like Growth Factors, Their Binding Proteins, and Prostate Cancer Risk: Analysis of Individual Patient Data from 12 Prospective Studies

Abstract

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 cancer.

Association between serum levels of insulin‐like growth factor‐1, bioavailable testosterone, and pathologic Gleason score

“…Serial reports from the Health Professionals Follow‐up Study (HPFS), a large prospective cohort study comprising 51 529 male health professionals from the United States, aged 40‐75 years at enrollment in 1986, demonstrate that circulating IGF‐1 level is positively associated with low‐grade, but not with high‐grade, prostate cancer 10, 11, 12. Associations between serum IGF‐1 level and low‐grade prostate cancer have also been shown by a pooled analysis of 12 prospective studies,13 and the results of other large prospective cohort studies, such as the Physicians’ Health Study (PHS) 14 and the European Prospective Investigation into Cancer and Nutrition (EPIC) study 15. These findings imply that there are stronger effects of IGF‐1 on the development of low‐grade prostate cancer than on the development of high‐grade disease.…”

Prevention and early detection of prostate cancer

“…For sex hormones, a pooled analysis of individual participant data from 18 studies found no significant associations 23 , but more data are needed to explore the relationship where both, decreased overall risk 23 and an increased risk of high-grade cancer have been reported 24 . For insulin-like growth factors (IGFs), a pooled analysis of individual participant data from 12 studies showed a significant positive association between circulating IGF-I and prostate cancer risk 25 ; more data are required on IGF-II and IGF binding proteins.…”

Hyperglycaemia-induced chemoresistance of prostate cancer cells due to IGFBP2

“…Metabolic disturbances also affect this axis, which is itself strongly associated with PCa (Monti et al 2007). Recent prospective epidemiology has consistently shown strong associations between circulating IGF1 levels and the subsequent risk of developing PCa (Roddam et al 2008). The actions of the IGFs are modulated by a family of high-affinity IGF-binding proteins (IGFBPs 1-6) that can either inhibit or enhance the actions of the IGFs.…”