Systematic review of the molecular basis of hereditary breast and ovarian cancer syndrome in Brazil: the current scenario

Abstract

Background: A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs. Although many studies have been conducted in Brazil, a global view on the molecular profile related to hereditary breast and ovarian cancer (HBOC) in this large and heterogeneous population is lacking.

Methods: A systematic review following the PRISMA guidelines was conducted in three electronic databases (PubMed, BIREME and SciELO). Brazilian studies covering molecular analysis of genes related to HBOC, published until December 2023, were considered.

Results: We identified 35 original studies that met all the inclusion criteria. A total of 137 distinct mutations were found in the BRCA1 gene, but four of them corresponded to 44.5% of all mutations found in this gene. The c.5266dupC BRCA1 mutation was responsible for 26.8% of all pathogenic mutations found in the BRCA1 gene in patients with clinical criteria for HBOC from the Brazilian population. Considering all studies that track this mutation in the BRCA1 gene, we found a frequency of 2% (120/6008) for this mutation in Brazilian patients. In the BRCA2 gene, the four most frequent mutations corresponded to 29.2% of pathogenic mutations. Even though it was tracked by few studies, the c.156_157insAlu mutation was responsible for 9.6% of all pathogenic mutations reported in the BRCA2 gene. Seventeen studies found pathogenic mutations in other non-BRCA genes, the c.1010G > A mutation in the TP53 gene being the most frequent one. Considering all studies that screened for this specific mutation in patients with the clinical criteria for HBOC, the frequency of c.1010G > A was estimated at 1.83% (61/3336).

Conclusions: Despite significant molecular heterogeneity among mutations in HBOC patients from Brazil, three mutations deserve to be highlighted, c.5266dupC, c.156_157insAlu and c.1010G > A in the BRCA1, BRCA2 and TP53 genes, respectively. With more than 200 records, these three mutations play a vital role in the pathology of breast and ovarian cancer in Brazil. The data collected shed light on the subject, but there is still not enough data from certain subpopulations.

Keywords: BRCA mutations; HBOC in Brazil; Hereditary breast and ovarian cancer; Systematic review.

Fig. 1

Flowchart representing the process of screening and selection of eligible studies, based on Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines [11]

Fig. 2

Geographical distribution of the studies included in this review according to the regions of Brazil. Each black line indicates the number of studies with samples from the respective region of the country (they are not distributed on the map according to the state or municipality localization). Red lines indicate the number of studies with samples from South and Southeast regions. The blue lines indicate studies that used populations from more than two regions (South, Southeast and Northeast). *Only two study included samples from all regions of the country

Fig. 3

Timeline showing the distribution of Brazilian studies and all methods used to track mutations in HBOC populations