Relationship between serum levels of insulin-like growth factors and subsequent risk of cancer mortality: Findings from a nested case-control study within the Japan Collaborative Cohort Study

Background: We investigated the association between serum levels of IGF-I, IGF-II, and IGFBP-3 and the subsequent risk of cancer mortality. Methods: Our case-control study examined samples from 914 cancer deaths and their 2739 matched controls within the Japan Collaborative Cohort Study. Blood samples were obtained at the baseline and stored at -80 °C until analysis for IGF-I, IGF-II, and IGFBP-3 levels. The conditional logistic model was used to estimate odds ratios (ORs) for cancer mortality associated with these serum levels. Results: The adjusted ORs for IGF-I quartiles ranged from 0.81 to 0.96 but were not significant. The adjusted ORs and 95% confidence interval (CI) for the second, third, and fourth IGF-II quartiles were 0.64 (95% CI: 0.52-0.79), 0.71 (95% CI: 0.58-0.88), and 0.73 (95% CI: 0.59-0.91), respectively, while those for the respective IGFBP-3 quartiles were 0.77 (95% CI: 0.63-0.96), 0.75 (95% CI: 0.60-0.94), and 0.71 (95% CI: 0.56-0.90). In the model of IGF-I, and IGF-II additionally adjusted for IGFBP-3, the associations of high IGFs levels were similar as observed in the above models, while the association of IGFBP-3 shifted into non-significance after adjusting for IGF-II. Conclusion: An increased level of IGF-II was significantly associated with decreased risk of cancer mortality, whereas the association between IGF-I and all cancer mortality was not significant. The inverse association of IGFBP-3 level with all cancer mortality was affected when adjusting for IGF-II levels, shifting from significant to non-significant. Confirmation of these results from further cohort studies may aid in identifying the potential association between these molecules and the risk of cancer among the general Japanese population.