Progesterone receptor gene polymorphism (PROGINS) in 701 women from a mammographic breast cancer screening program (NMPOA) in Southern Brazil

Abstract

21048 Background: Several genetic polymorphisms in hormone receptor genes have been associated with breast cancer (BC) risk. Among these, a 306 base-pair insertion of the Alu subfamily in intron 7 of the progesterone receptor (PR) gene, (PROGINS), has been associated with decreased BC risk in several populations. In Brazil, BC is a significant public health problem, due to its high incidence and mortality rates. In Porto Alegre, Brazil`s southernmost capital, a multidisciplinary Breast Cancer Prevention Project - the Nucleo Mama Porto Alegre Cohort (NMPOA) was started in 2004 and includes a mammographic screening program for women ages 40–69 years. Goal: Determine the allelic and genotypic frequencies of PROGINS in women undergoing annual BC screening and correlate its presence with mammography results and presence of additional BC risk factors (family history of BC, body mass index, estimated BC risk by the Gail model and age) at baseline and after 10 years. Methods: A sample of 701 women from the NMPOA BC screening program was consecutively enrolled in the study from November/2005 until March/2006. Clinical data, mammography results (as BIRADS categories) and BC risk information was obtained by chart review. PROGINS genotyping was performed by polymerase chain reaction (PCR). Results: Of the 701 patients studied, 504 (71,0%) were wild-type homozygous, 184 (26,2%) heterozygous and 13 (1,8%) homozygous for the PROGINS polymorphism. These genotypic frequencies are similar to those of other reports in different populations. Genotype was correlated with 5-year and vital BC risk estimates (Gail model), body mass index, family history of BC and mammography findings. A statistically significant association was found between the presence of PROGINS and a positive family history of BC (p< 0,05). Conclusions: The genotypic and allelic frequencies of the PROGINS polymorphism were not significantly different from those reported previously for other populations. Prospective clinical evaluation of the women followed in this program and correlation of genotype with clinical findings may be important to elucidate additional risks associated with the PROGINS polymorphism. No significant financial relationships to disclose.