Abstract
In Brazil, breast cancer is a public health care problem due to its high incidence and mortality rates. In this study, we investigated the prevalence of hereditary breast cancer syndromes (HBCS) in a population-based cohort in Brazils southernmost capital, Porto Alegre. All participants answered a questionnaire about family history (FH) of breast, ovarian and colorectal cancer and those with a positive FH were invited for genetic cancer risk assessment (GCRA). If pedigree analysis was suggestive of HBCS, genetic testing of the BRCA1, BRCA2, TP53, and CHEK2 genes was offered. Of 902 women submitted to GCRA, 214 had pedigrees suggestive of HBCS. Fifty of them underwent genetic testing: 18 and 40 for BRCA1/BRCA2 and TP53 mutation screening, respectively, and 7 for CHEK2 1100delC testing. A deleterious BRCA2 mutation was identified in one of the HBOC probands and the CHEK2 1100delC mutation occurred in one of the HBCC families. No deleterious germline alterations were identified in BRCA1 or TP53. Although strict inclusion criteria and a comprehensive testing approach were used, the suspected genetic risk in these families remains unexplained. Further studies in a larger cohort are necessary to better understand the genetic component of hereditary breast cancer in Southern Brazil.
Highlights
Breast cancer (BC) is a significant health care problem worldwide, and approximately 1.67 million new casesAn estimated 5-10% of all BCs are hereditary, i.e. caused by germline mutations in high-penetrance cancer predisposition genes (King et al, 2003)
Of the 1,247 patients referred to genetic cancer risk assessment (GCRA), 902 (72.3%) effectively participated in the assessment and of these, 214 (23.7%) women from 183 families fulfilled criteria for one or more of the breast cancer predisposition syndromes (BCPS) considered in our study: 65 fulfilled criteria for hereditary breast and ovarian cancer (HBOC), 122 for LFL and 22 for HBCC syndromes
Eight families were tested for BRCA1/BRCA2 and TP53 germline mutations, two families for BRCA1/BRCA2 and CHEK2 mutations, three families for TP53 and CHEK2 mutations, and one family was screened for mutations in all four genes (BRCA1/BRCA2, CHEK2 and TP53)
Summary
Breast cancer (BC) is a significant health care problem worldwide, and approximately 1.67 million new casesAn estimated 5-10% of all BCs are hereditary, i.e. caused by germline mutations in high-penetrance cancer predisposition genes (King et al, 2003). The more prevalent mutations are in BRCA1 (OMIM#113705) and BRCA2 (OMIM#600185) (Miki et al, 1994; Wooster et al, 1994), tumor suppressor genes which are associated with hereditary breast and ovarian cancer (HBOC) syndrome. Large genomic deletions and duplications involving one or more exons of BRCA1, and less commonly, BRCA2, have been reported (Gutiérrez-Enríquez et al, 2007; PreislerAdams et al, 2006; Thomassen et al, 2006). Most of these mutations are caused by recombination events involving Alu repeats that are numerous in the BRCA1 locus (Payne et al, 2000). Other studies have screened cohorts of Brazilian BC patients for specific mutations, or have focused on some subgroups (for example young women) (Carraro et al, 2013; Ewald et al, 2011; Gomes et al, 2007) but the exact prevalence of any BRCA mutation remains largely unknown
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