Adrenal-permissive HSD3B1 genetic inheritance and risk of estrogen-driven postmenopausal breast cancer.

10503 Background: Genetic factors that contribute to endogenous estrogen synthesis and postmenopausal breast cancer risk are unknown. We set out test the hypothesis homozygous inheritance of common 1245A→C missense-encoding polymorphism in HSD3B1, which is (8-10%) White populations, functionally adrenal permissive increases aromatase substrate, androstenedione, associated with receptor-positive cancer. Methods: A prospective single institution study receptor-driven for determination HSD3B1 genotype, circulating steroid concentrations, adrenal-permissive genotype frequency compared general population receptor-negative Validation was performed 2 genomic studies receptor documentation. The primary outcome population. Genotype comparisons were also done association androgen concentrations determined. Results: validation had 199 1628 women, respectively. women estrogen-driven cohort 17.5% (21/120) 9.6% (429/4451) [p = 0.0077]. validated using Cambridge TCGA datasets together: 14.4% (56/389) 6.0% (9/149) (p 0.007) 0.005). Circulating androstenedione concentration significantly higher other genotypes 0.03). Conclusions: These findings link genetic exposure have broad implications stratification, prevention, potential biomarkers hormonal therapy response possibly clinical outcomes related physiology women.