Detection of Inherited Mutations in Brazilian Breast Cancer Patients Using Multi-Gene panel Testing

Abstract Genetic diversity of germline variants in breast cancer (BC) predisposition genes, is unexplored in miscegenated people, such as Latin American populations. We evaluated 1,662 Brazilian BC patients, who underwent hereditary multi-gene panel testing (20–38 cancer susceptibility genes), to determine the spectrum and prevalence of (likely) pathogenic variants (P/LP) and variants of uncertain significance (VUS). In total, 161 (9.7%) participants carried germline P/LP variants in BRCA1/2 and 162 (9.7%) in other cancer predisposition genes. Overall, 341 distinctive P/LP variants were identified in 22 genes, including BRCA1(28%), BRCA2(19%), TP53(11%), MUTYH heterozygous (10%), ATM(9%), CHEK2(6%), and PALB2(5%). The Brazilian variant TP53 R337H (c.1010G > A, p.Arg337His), detected in 1.6% of BC patients and 0.09% of reference controls (RC), was strongly associated with odds of disease (OR = 17.67; 95%CI:9.21–34.76; p < 0.001). Heterozygous MUTYH c.1187G > A and MUTYH c.536A > G, detected in 0.78% (0.90% RC) and 0.48% (0.40% RC) of the patients, respectively, were not associated with the odds of BC, the former with OR = 0.87 (95%CI:0.49–1.53; p = 0.63) and the latter with OR = 1.20 (95%CI:0.58–2.49; p = 0.63). Besides, 766 individuals (46.1%) had 1 or more VUS. Concluding, the use of multi-gene panel testing doubled the identification of mutation carriers in Brazilian BC patients. Special attention should be given to TP53 mutations.