The spectrum of BRCA1 and BRCA2 alleles in Latin America and the Caribbean: a clinical perspective

Abstract

Hereditary cancer predisposition gene testing allows the identification of individuals at high risk of cancer that may benefit from increased surveillance, chemoprevention, and prophylactic surgery. In order to implement clinical genetic strategies adapted to each population's needs and intrinsic genetic characteristic, this review aims to present the current status of knowledge about the spectrum of BRCA pathogenic variants in Latin American populations. We have conducted a comprehensive review of 33 studies published between 1994 and 2015 reporting the prevalence and/or spectrum of BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) variants. The combined sample size for these studies consisted of 4835 individuals from 13 countries in Latin America and the Caribbean, as well as in Hispanics in the United States. A total of 167 unique pathogenic variants have been reported in the existing literature. In unselected breast cancer cases, the prevalence ranged from 1.2 to 27.1%. Some countries presented a few recurrent pathogenic variants, while others were characterized by diverse, non-recurrent variants. The proportion of BRCA pathogenic variants shared between Hispanics in the United States and Latin American populations was estimated at 10.4%. Within Latin America and the Caribbean, 8.2% of the BRCA variants reported were present in more than one country. Countries with high prevalence of BRCA pathogenic variants may benefit from more aggressive testing strategies, while testing of recurrent variant panels might present a cost-effective solution for improving genetic testing in some, but not all, countries.

Keywords: BRCA1; BRCA2; Breast cancer; Genetic testing; Hereditary; Hispanics; Latin America.

Fig. 1

The network of recurrent BRCA1 (a) and BRCA2 (b) pathogenic variants reported in Latin America, the Caribbean, and US Latinos. Recurrent variants have been reported more than once within a country and/or have been observed in more than one country. The connections between the nodes generate a complete system of interactions between variants and the countries in which they have been detected. The nodes representing the countries are mapped on the network based on the proportion of shared variants with other Latin America countries. The size of the nodes representing the variants is proportional to the total number of observations, dashed edges were used for recurrent variants that were unique to a country, and thicker edges indicate variants that are shared in more countries. The blue node colors indicate countries for which at least one study conducted comprehensive BRCA1/2 analysis by direct sequencing, and the green nodes indicate countries for which BRCA analysis was conducted using mutation panels or indirect analysis methods. Darker nodes (dark blue or dark green) indicate countries for which at least one study conducted comprehensive large rearrangement screening, while the pale node colors (pale blue or pale green) indicate countries for which no comprehensive rearrangements were assessed. The network was generated with Cytoscape 3.2.1 [96]