Abstract P2-13-01: The Brazilian founder TP53 p.R337H mutation is uncommon in Portuguese women diagnosed with breast cancer

Abstract

Abstract Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern regions of Brazil, both in the general population and in patients from high risk breast cancer families with adrenocortical, choroid plexus and breast carcinomas, there has been controversy on the origin of this mutation. Preliminary analysis of the small subset of Brazilian mutation carriers that defined the founder haplotype using 29 tag SNPs revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families (one Portuguese and one German) (Chompret et al., 2000; Herrmann et al. 2012). Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer in Southern Brazil are p.R337H carriers, we initiated TP53 genotyping in a Portuguese cohort of women with breast cancer recruited from the cities of Lisboa and Braga. Median age at diagnosis of breast cancer among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening was performed using Real-Time PCR (taqman assays), and failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study of 815 breast cancer-affected women from Southern and Southeastern Brazil, which has reached frequencies of 12.1 and 5.1% in pre- and post-menopausal women, respectively (Ashton-Prolla et al. 2012; ASCO Annual Meeting, ref 1522). We conclude that there is a significant difference in mutation frequency observed between the two cohorts (p<0.001). These findings suggest that TP53 p.R337H is not a common molecular alteration in Portuguese breast cancer-affected patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-13-01.