Genetic variants, prediagnostic levels of insulin-like growth factors, insulin and glucose, and the risk of colorectal cancer: The Multiethnic Cohort Study
Couplée aux données de la cohorte multiethnique, cette étude américaine (1 954 cas et 2 587 témoins) évalue l'association entre 5 variants génétiques associés aux facteurs de croissance analogues à l'insuline, à l'insuline ou au glucose et le risque de cancer colorectal
Background: Increased exposure of colonic and rectal epithelial cells to the pro-mitotic and anti-apoptotic effects of insulin and insulin-like growth factors (IGFs) is hypothesized to increase colorectal cancer risk. Methods: In a case-control study nested within the Multiethnic Cohort, we attempted to replicate associations for five genetic variants associated with IGF-system biomarkers, insulin, or glucose and to examine their association with the risk of colorectal cancer. In a subset of participants, the association between circulating biomarkers and colorectal cancer risk was examined. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for genetic variants (1,954 cases / 2,587 controls) and serum biomarkers (258 cases / 1,701 controls). Results: Associations with circulating biomarkers were replicated in the MEC for IGF1 rs35767 and for IGFBP3 rs2854744, rs2854746, and rs3110697 (p < 0.05). Homozygous carriers of the GCKR rs780094 variant T-allele were at a decreased risk of colorectal cancer (OR =0.77 [0.64-0.92]). In risk factor adjusted models, participants with the highest prediagnostic IGF-II levels were at an increased risk (OR T1 vs. T3 =1.58 [1.09-2.28]; p for trend = 0.011) and participants with the highest prediagnostic IGFBP-3 levels were at a decreased risk of colorectal cancer (OR = 0.53 [0.34-0.83]; p for trend = 0.003). Conclusion: These data provide further support for a role of prediagnostic IGF and insulin levels in the etiology of colorectal cancer. Impact: Future studies attempting to replicate the association between the GCKR rs780094 variant and the risk of colorectal cancer are warranted.