Screening for germline mutations in families at-risk for hereditary breast cancer in Southern Brazil

Abstract

22128 Background: In this study, we investigated the prevalence of hereditary breast cancer (HBC) syndromes and of germilne mutations in breast cancer predisposition genes, in a population-based cohort of women attending primary health care units in Brazil´s southernmost capital, Porto Alegre. Methods: All women were submitted to a questionnaire about family history (FH) of breast, ovarian and colorectal cancer. Those with a positive FH were invited for genetic cancer risk assessment (GCRA). If pedigree analysis elicited criteria for the major HBC syndromes (hereditary breast and ovarian cancer, hereditary breast and colorectal cancer, and Li-Fraumeni/Li- Fraumeni-like syndromes), genetic testing was offered to the family, including BRCA1, BRCA2, TP53, and CHEK2 mutation analysis. Results: Of 902 women submitted to GCRA, 214 (23.7%) women from 183 families had pedigrees suggestive of HBC. Fifty of these families underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 germline mutations, respectively, and 7 for the CHEK2 1100delC mutation. No known deleterious mutations were identified in the HBOC families. In the LFL group, the R273C mutation was found in one family. The CHEK21100delC mutation was found in one of the seven families with hereditary breast and colorectal cancer phenotype. Conclusions: In spite of the relatively strict inclusion criteria, aimed at testing high risk families for HBC, the risk posed to most of these families remains unexplained. To our knowledge this is the first report of the prevalence of HBC phenotypes and germline mutations in corresponding breast cancer predisposition genes in a sample of at-risk individuals identified in a community-based cohort in South America. No significant financial relationships to disclose.