Nested case-control study of the association of circulating levels of serum insulin-like growth factor I and insulin-like growth factor binding protein 3 with breast cancer in young women in Norway

Background: High circulating levels of insulin-like growth factor (IGF-I) may elevate the risk of breast cancer in premenopausal women, possibly by increasing cell proliferation and reducing apoptosis. Methods: We conducted a nested case-control study among 35,105 Norwegian women who participated in a health screening survey, ages 40 to 42 years, and who were subsequently followed for a mean period of 4.3 years. During this period, 325 women were diagnosed with breast cancer; 647 women without breast cancer, matched on age and time of blood sampling, were selected as controls. Serum concentrations of IGF-I and its main binding protein (IGFBP-3) were measured with radioimmunoassay, and logistic regression analysis was used to adjust for relevant covariates. Results: The mean age at blood collection was 41.1 years in both groups, and the mean age at diagnosis for the cases was 45.4 years (range, 40-51 years). The median IGF-I level did not differ between cases (205 ng/mL) and controls (202 ng/mL). When analyzed by categories of serum IGF-I, the relative risk for women in the highest versus the lowest quintile was 1.46 (95% confidence interval, 0.93-2.32; P(trend) = 0.15) after adjusting for serum IGFBP-3, age, and year of blood collection. The exclusion of cases that were diagnosed within 2 years after blood collection did not materially affect the results. Conclusion: We found only a modest positive association between serum IGF-I levels and risk of breast cancer in women younger than 50 years of age.