Prostate Cancer Risk in Relation to Insulin-like Growth Factor (IGF)-I and IGF-Binding Protein-3: A Prospective Multiethnic Study

Abstract

IntroductionDespite its importance (1, 2), relatively little is known about prostate cancer etiology (3,4). Risks are highest among North American Blacks and lowest in Asians, whereas Whites seem to lie in between (5). Levels of insulin-like growth factor (IGF)-I have been associated with increased risk of prostate cancer (6-10), but other well-designed studies have reported null results (11-13). Studies of IGF-binding protein-3 (IGFBP-3) have reported both increased (12) and decreased risk of prostate cancer (8, 13) as well as no association (9-11). Inconsistent results suggest additional factors, including but not limited to methodologic differences, unmeasured confounding variables, and differences in ethnic diversity of populations. Our purpose was to determine the associations between prediagnostic levels of IGF-I and IGFBP-3 and risk of prostate cancer, and our multiethnic population provided the opportunity to explore the role ethnicity might play. Materials and MethodsAs part of the original case-control study (14)(15)(16)(17), from 1990 to 1992, healthy male controls were matched to cases by age, region, and ethnicity. Participants were asked to fast for 12 h before blood specimen collection, and to the extent possible, specimens were collected early in the morning. Of the 1,121 specimens (40 mL of venous blood), adequate sample remained on 1,012 subjects. Outcome ascertainment was conducted by linkage to state and provincial cancer registries and vital statistics data in California (United States), Hawaii (United States), and British Columbia (Canada). Prostate cancer occurred 1 or more years after blood draw in 96 men with enough sera for analysis. Men known to be alive and free of prostate cancer when the case was diagnosed were matched by ethnicity (White, Black, Chinese, and Japanese), region (Los Angeles, San Francisco, Hawaii, and Vancouver), and 5-year age category in a ratio of four controls per case (n = 416). Ethical approval was given by the University of British Columbia Research Ethics Board.For each subject, a 1.0-mL vial of serum was removed from storage, packed in dry ice, and shipped to the laboratory of one of us (M.D.P.) at the Lady Davis Institute for Medical Research (Montreal, Quebec, Canada). Laboratory staff used ELISA (Diagnostic Systems Laboratories, Inc.) to analyze samples, blinded to ethnicity and case-control status. Samples were assayed twice, and the mean was used for analysis.Spearman correlation coefficients were used to examine relationships between serum measurements and potential confounders [age at blood draw; waist circumference; weight; Quetelet's index (kg/m 2 ) or body mass index; daily dietary intake of calories, protein, carbohydrates, fat, calcium, vitamin D, and alcohol; daily hours sitting or in vigorous activity; serum levels of C-peptide, sex hormone -binding globulin, prostate-specific antigen, cholesterol, total testosterone, percentage free testosterone, and dihydrotestosterone; and family history of prostate cancer]. The change-in-estimate criterion ...

Blood cadmium levels increase prostate specific antigen and insulin-like growth factor-1 among cadmium exposed workers

“…These resultswere different from those of Borugian et al (24) who observed no association of prostate cancer risk with prediagnostic IGFIand a positive association with prediagnostic IGFBP-3 and prostate cancer, but only for the subgroup of black males and only in the third quartile. The interaction between IGF-I and IGF-IR is regulated by the IGF-binding proteins (IGFBPs), IGFBP-3 being the most abundant.…”

Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and single nucleotide polymorphism in PSA and CYP17 gene may contribute to early diagnostics of prostate cancer

“…Contrary to study by Stattin et al [5] and Rowlands et al [24], however, consistently with studies by Aksoy et al [ Severi et al [24] , Borugian et al [13], Sciarra et al [25] we did not confirm increased serum level of IGF1 in individuals with PCa. Similar to Severi et al [24] findings, the risk of PCa did not increase even for serum level of IGF1 over 95% CI of normal range.…”

“…Numerous studies have concerned the association between serum level of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) and IGF-1/IGFBP-3 molar ratio, but the results are somehow contradictory [11,12,13,14,15,16,17,18].…”

Tea Polyphenols Decrease Serum Levels of Prostate-Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor In vitro

“…A recent study concluded that there was no association between levels of these two proteins and prostate cancer, although interestingly, the authors noted that prediagnostic levels of IGFBP-3 correlated with prostate cancer risk, but only for Black men (56).…”