Interactions of the Insulin-Like Growth Factor Axis and Vitamin D in Prostate Cancer Risk in the Prostate Cancer Prevention Trial

Some, but not all, epidemiologic studies report an association between vitamin D and prostate cancer risk. The inconsistent findings might be explained in the context of modification by members of the insulin-like growth factor (IGF) axis. Data and specimens for this nested case-control study (n = 1695 cases and n = 1682 controls) are from the Prostate Cancer Prevention Trial (PCPT). Baseline serum samples were assayed for 25(OH)D, IGF-1, IGF-2, IGFBP-2, IGFBP-3, and the ratio of IGF1: BP3, along with insulin-related markers c-peptide and leptin. The presence of prostate cancer was assessed by prostate biopsy. Multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for prostate cancer risk. There were no interactions between serum 25(OH)D and IGF analytes in relation to prostate cancer risk when PCPT treatment arms were combined. In the placebo arm, above median serum 25(OH)D levels were associated with increased risk of prostate cancer among men with higher IGF-2 (OR: 1.33, 95% CI: 1.00-1.65), with a significant interaction between 25(OH)D and treatment arm (P-interaction = 0.04). Additionally, there was an interaction between treatment arm and serum IGFBP-3 (P-interaction = 0.03). Higher serum 25(OH)D may increase risk of prostate cancer in the presence of higher circulating IGF-2.