Abstract PR-04: Interactions between plasma levels of 25-hydroxyvitamin D and insulin-like growth factor (IGF)-1, IGF-binding proteins and C-peptide with risk of colorectal cancer

Abstract

Abstract Background: Vitamin D status and levels of insulin-like growth factor (IGF)-1 and C-peptide (a marker of insulin exposure) have been implicated in colorectal carcinogenesis. However, IGF-1 is not an easily modifiable risk factor. Laboratory studies have suggested that 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D may play a role in the regulation of IGFBP3, the major binding protein for IGF-1, suggesting that some of the cancer promoting effects of IGF-1 may be modified by vitamin D. Methods: We examined additive and multiplicative interactions between plasma 25-hydroxyvitamin D (25(OH)D) levels and components of the IGF axis (IGF-1, IGFBP3, IGFBP1) as well as C-peptide levels combining data from two large U.S. cohorts, the Health Professionals Follow up Study (HPFS) and the Nurses’ Health Study cohort (NHS). 365 cases (NHS: 191 cases diagnosed between 1990-2000; HPFS: 174 cases diagnosed between 1993-2002) were matched to 727 controls by age, fasting status (NHS only) and month and year of blood donation. For the various analytes, being high or low was based on being either above (or equal) or below the medians, respectively. Results: Individuals with high IGF-1/IGFBP-3 molar ratio, C-peptide levels, or low 25(OH)D levels were at elevated risk for colorectal cancer. Compared to participants with high plasma 25(OH)D levels and low IGF-1/IGFBP-3 ratio (reference group), participants with a high IGF/IGFBP-3 ratio had an odds ratio (OR) of 1.38 (95% CI: 0.90 to 2.12) for colorectal cancer when 25(OH)D levels were high and an OR of 2.65 (95% CI: 1.74 to 4.04) when 25(OH)D levels were low (p(interaction): additive = 0.02, multiplicative = 0.25). Also, for colon cancer, among individuals with high C-peptide levels, risk was elevated when 25(OH)D levels were low (OR = 2.15, 95% CI: 1.26 to 3.65) but not when 25(OH)D levels were high (OR=1.08, 95% CI=0.63 to 1.85) (p(interaction); additive = 0.04; multiplicative = 0.18). Conclusion: The results from this study suggest that improving vitamin D status may help lower risk of colorectal cancer associated with higher IGF-1/IGFBP3 ratio or C-peptide levels. Citation Information: Cancer Prev Res 2010;3(12 Suppl):PR-04.