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Insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been positively associated with breast cancer, especially among premenopausal women. Hispanic women have lower levels of IGF-1 and IGFBP-3 than non-Hispanic white (NHW) women, although no studies have adequately assessed the relationship among IGF-1, IGFBP-3, and breast cancer in Hispanic women. We investigated the association among IGF-1, IGFBP-3, and breast cancer within a subset of participants (n = 184 cases, 522 controls) of a population-based case-control study of women living in the U.S. Southwest. Serum levels of IGF-1 and IGFBP-3 were measured in fasting blood samples, and associations among IGF-1, IGFBP-3, and breast cancer were calculated using logistic regression, adjusting for age, study center, ethnicity, education, recent hormone exposure, body mass index, parity, total energy expenditure, total calories, and cholesterol. Both IGF-1 and IGFBP-3 were statistically significantly associated with breast cancer overall (highest vs. lowest quartile (Q4 vs. Q1) for IGF-1: odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.07-3.43); for IGFBP-3: OR = 3.04, 95% CI = 1.63-5.67). Positive associations were observed for both premenopausal breast cancer and postmenopausal breast cancer. IGF-1 was associated with breast cancer in NHW women (Q4 vs. Q1: OR = 2.82, 95% CI = 1.36-5.83), but not in Hispanic women (Q4 vs. Q1: OR = 0.81, 95% CI = 0.29-2.27). IGFBP-3 was associated with breast cancer in both ethnic groups (Q4 vs. Q1 for NHW: OR = 3.32, 95% CI = 1.45-7.60; Q4 vs. Q1 for Hispanics: OR = 2.15, 95% CI = 0.76-6.04). In conclusion, the association between IGF-1 and breast cancer differed by ethnicity, while no ethnic differences were observed in IGFBP-3-associated breast cancer.