Clinical Factors Associated with High Mammographic Density in Postmenopausal Women and their Relationship with Dinucleotide Gtn Repeat Polymorphism in the Estrogen Receptor Alpha Gene

Abstract

Introduction: Epidemiological evidence shows that variations in estrogen receptor (ER) genes cause alterations in the effect of estrogen in breast tissue, which may explain individual variations in mammographic density. High mammographic density (HMD) is an important risk factor for breast cancer. Objective: To evaluate the association of clinical features and polymorphism of ERα-(GT)n gene and mammographic density in post-menopause women. Casuistry and method: According to ACR-BIRADS criteria, 463 post-menopause women of ages between 45 and 60 have been prospectively analyzed through computer objective assessment, being 308 with HMD and 155 with non-dense breasts (Control group). The participants had not used hormone therapies 12 months prior to assessments and had no personal history of breast cancer. Risk factors for breast cancer considered by other studies also have been analyzed in this paper. Peripheral blood samples have been obtained to extract DNA and to analyze the presence of polymorphism in the ERα-(GT)n promoter region. Results: From the risk factors considered for breast cancer, there was association with high mammographic density in: age (p=0.005); waist circumference (p=0.001); number of pregnancies (p=0.007); age at 1st birth (p=0.035); family history (p=0.035); time after menopause (p=0.007), and body mass index (p=0.022). Differences between HMD and controls for distribution of tanden repeats polymorphism genotype STRs-(GT)n (p=0.151) was verified as non-significant. Conclusion: Our data showed that age, waist circumference, number of pregnancies, age at 1st birth, family history of breast cancer, time after menopause, and body mass index were associated to post-menopause HMD. However, tanden repeats polymorphism (GT)n may not be associated with HMD but it will be necessary studies with a larger number of cases as we have obtained few genotypes (GT)n higher than 17 repeats.