Evaluation of the synergistic effect of insulin resistance and insulin-like growth factors on the risk of breast carcinoma

BACKGROUND. The purpose of the current study was to investigate the association between insulin resistance (which was measured using fasting blood C-peptide) and its joint association with insulin-like growth factors (IGF-1, IGF-2, and IGF binding protein-3 [IGFBP-3]) on the risk of breast carcinoma. METHODS. included in the current study were 400 case-control pairs from the Shanghai Breast Cancer Study. Pretreatment biospecimens and interview data were collected from all breast carcinoma cases and their individually matched controls. RESULTS. Breast carcinoma risk was found to be statistically significantly increased when higher blood levels of C-peptide and IGFs were noted in a dose-response manner. There was a statistically significant twofold to threefold increased risk of breast carcinoma for women in the highest quartile of C-peptide, IGF-1, or IGFBP-3 compared with women in the lowest quartiles. Women with high levels of both C-peptide and IGF-1 or IGFBP-3 also were found to have a substantially higher risk of breast carcinoma than those women with a high level of only one of these molecules. The adjusted odds ratios (ORs) were 3.79 (95% confidence interval [95% CI], 2.03-7.08) for those with a higher level of both C-peptide and IGF-1 and 4.03 (95% CI, 2.06-7.86) for those with a higher level of both C-peptide and IGFBP-3. CONCLUSIONS. The results of the current study suggest that insulin resistance and IGFs may synergistically increase the risk of breast carcinoma. Cancer 2004;100: 694-700. (C) 2004 American Cancer Society.