Abstract Abstract #5003 Background: With the human genome studies, knowledge about polymorphisms started raising interest in a variety of fields and, in medicine, the evidence of direct action of polymorphisms on the arising and progression of diseases, disclosing the possibility of using them as disease predisposition markers. Substitutions, insertions or deletions which are transmitted through generations and reach frequencies equal or superior to 1% in the population are named polymorphisms. Knowing that the mammographic pattern is a multifactorial character, the objectives of this study were to evaluate a possible association of clinical characteristics and polymorphisms HaeIII, MspI and XbaI of the estrogen receptor gene alpha with postmenopausal mammary density. Materials and Methods: A prospective evaluation was made of 120 women who were not hormone therapy users and had no clinically or mammographically identified breast lesions. All of them underwent bilateral mammography, and the radiological density was determined by three independent observers, with two subjective evaluations based on the ACR-BIRADS® classification of mammographic patterns, 2003, and one computerized evaluation – the grey-scale histogram tool of the Adobe Photoshop® 7.0 software. Peripheral blood samples were obtained for DNA extraction, performed according to the GFX® Kit protocol from Amersham-Pharmacia. After DNA extraction, PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was carried out for an analysis of the polymorphisms present in intron 1 (HaeIII and XbaI) and in exon 1 (MspI) of the estrogen receptor gene. Results: There was a high degree of concordance among the observers in the determination of mammary density (Kappa, Pearson and Spearman - p<0.001). The associations of clinical characteristics with mammary density were: age (p=0.04), body mass index (p<0.0001), age at menarche (p=0.02), age at menopause (p=0.120), age at first delivery (p=0.120), parity (p=0.09). The relation between the allele distribution of the polymorphisms and the density was: XbaI (p=0.02), HaeIII (p=0.65), and MspI (p=0.65). Conclusion: Polymorphism XbaI and the clinical factors age, menarche and body mass index showed to be associated with postmenopausal mammary density. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5003.