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Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, 4001 Old Clinic Building, CB 7570, Chapel Hill, NC, 27599-7570, USA, dr.jykim76@gmail.com.
Purpose:
Major clinical characteristics of BRCA1/2-related cancers include association with estrogen and metabolic consequences. We aimed to evaluate serum estradiol (E2) and insulin-like growth factor 1 (IGF-1) levels as a marker of insulin resistance in BRCA1/2 mutation carriers and high-risk, BRCA-negative controls.
Methods:
Eligible cancer-free women (age 18-42 with regular menstrual cycles) who had been screened for BRCA1/2 mutations between 2005 and 2013 completed a questionnaire and underwent a single blood draw. E2 was measured with radioimmunoassay, and IGF-1 was measured with enzyme-linked immunosorbent assay.
Results:
Eighty-six women participated (44 carriers and 42 non-carriers) in this study. BRCA mutation carriers were significantly younger than non-carriers (p = 0.0002). Age-adjusted basal (menstrual cycle days 2-5) serum E2 level was not significantly different between BRCA mutation carriers and non-carriers (30.4 vs. 24.7 pg/mL, p = 0.07). BRCA mutation carriers have significantly lower age-adjusted serum IGF-1 levels compared to non-carriers (89.7 vs. 112.6 ng/mL, p < 0.001). In women with BRCA mutations, the risk of having low serum IGF-1 level (IGF-1: ≤85 ng/mL) was 10.7 times as great as that of women without BRCA mutations (95 % CI 2.5, 46.2). There was a significant inverse association between basal E2 and IGF-1 levels in BRCA mutation carriers after adjusting age and BMI (p = 0.03).
Conclusions:
IGF-1 level is significantly lower in cancer-free BRCA mutation carriers versus BRCA-negative controls, and there is a potential association between E2 and IGF-1 in cancer-free BRCA mutation carriers. Our findings may instigate future studies evaluating the role of both E2 and IGF-1 in BRCA mutation carriers.
