Genes Associated With Serum Estrone, Estrone Conjugates, And Androstenedione Concentrations In Postmenopausal Women With Estrogen Receptor-Positive Breast Cancer.

593 Background: Estrone (E1), the predominant estrogen in postmenopausal women, is synthesized from androstenedione (A) in the ovaries and adipocytes and can be converted to conjugates (E1Cs). Both circulating E1 and E1Cs are known risk factors for breast cancer; and E1C is present at concentrations up to 10 fold higher in breast cancer tissue than in serum. However, little is known regarding the genes that regulate serum A, E1 or E1Cs concentrations. Methods: In a cohort of 776 postmenopausal women with estrogen receptor positive breast cancer, we used a genome-wide association study (GWAS) to identify SNP signals associated with these concentrations. Serum levels of each hormone were measured using GC-MS/MS, and patients were genotyped at ~600,000 SNPs and another 7 million were imputed. Using linear regression models with additive genetic effects, a GWAS was conducted for each hormone level separately as well as the ratio of E1/A, E1Cs/A and E1Cs/E1. SNP effects were adjusted for BMI, population strati...