Division of Medical Genetics University of Washington, Seattle 98195-7720, USA. schubert@u.washington.edu
In order to evaluate the role of inherited variation in the estrogen receptor (ESR1) gene in human breast cancer, we determined intronic sequences flanking each ESRI exon; identified multiple SNPs and length polymorphisms in the ESR1 coding sequence, splice junctions and regulatory regions; and genotyped families at high risk of breast cancer and population-based breast cancer patients and controls. Of 10 polymorphic sites in ESR1, four are synonymous SNPs, two are nonsynonymous SNPs and four are length polymorphisms; five are novel. No ESR1 polymorphisms were associated with breast cancer, either in the high-risk families or the case-control study. We therefore conclude that inherited genetic variation is not a mechanism by which the estrogen receptor is commonly involved in breast cancer development.