Abstract
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.