Abstract PR-1: Genetic African ancestry and race differences in blood insulin-like growth factor 1 (IGF-1), IGF-2, and IGF binding protein 3 (IGFBP-3)

Abstract

Abstract Purpose: We have previously reported that African American women have significantly higher IGF-1 levels, and lower IGF-2 and IGFBP-3, compared to white women. This investigation aims to determine if genetic African ancestry is associated with these racial differences in blood IGF levels. Methods: The Southern Community Cohort Study (SCCS) is a prospective cohort study of 86,000 men and women, with two-thirds African American recruitment, designed to investigate racial disparities in cancer. We randomly selected 1000 African American and 1000 non-Hispanic white female participants to support focused investigations of racial differences in biomarkers possibly related to breast cancer. Serum IGF-1, IGF-2, and IGFBP-3 levels were measured by ELISA. We estimated African and European admixture using a panel of 276 ancestry informative genetic markers. Final analyses included 821 African American women and 816 white women after excluding women taking hormone replacement therapy or insulin for diabetes. White women had a low African ancestry (median = 0.4%, range=0.1 % to 17.1 %) and thus were considered as a single ancestry category. For African Americans, cutpoints of <85% (n=149), 85%-95% (n=230), and ≥95% (n=442) defined “low,” “medium,” and “high” African ancestry. Using multivariable linear regression, we estimated differences in IGF levels across ancestry categories while adjusting for age, body mass index (BMI), height, menopausal status, and BMI at age 21 years. Results: African American women having 85% African ancestry. For example, IGF-2 levels among white women and African American women with <85%, 85%-95%, and ≥95% African ancestry were 1771.9 ng/ml, 1713.5 ng/ml, 1620.3 ng/ml, and 1620.6 ng/ml, respectively. African American women with < 85% African ancestry had IGF-2 levels that were about 5.8% higher than African American women with 85%-95% (p=0.03) or ≥95% (p=0.01) ancestry. IGF-1 levels among white women and African American women with <85%, 85%-95%, and ≥95% African ancestry were 134.7 ng/ml, 143.8 ng/ml, 147.8 ng/ml, and 147.4 ng/ml, respectively, while IGFBP-3 levels were 3871.8 ng/ml, 3816.9 ng/ml, 3629.0 ng/ml, and 3693.9 ng/ml, respectively. African American women with 85% African ancestry, but these differences in IGF-1 and IGFBP-3 levels between African American ancestry groups were not statistically significant. We also calculated the molar ratio of IGF-1 to IGFBP-3 as an index of biologically available or free IGF-1. Differences in free IGF-1 among white women and African American women with <85%, 85%-95%, and ≥95% African ancestry were 0.126,0.137,0.148, and 0.145, respectively. Free IGF-1 levels were significantly lower among African American women with <85% compared to women with 85%-95% (p=0.02) or ≥95% (p=0.05) ancestry. Conclusion: Estimates of African ancestry are significantly associated with IGF-2 and free IGF-1, and suggest inherited genetic traits associated with African ancestry contribute to racial differences in IGF levels. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):PR-1.