Germline variants in hereditary breast cancer genes are associated with early age at diagnosis and family history in Guatemalan breast cancer

• Published in: Breast cancer research and treatment Vol. 189; no. 2; pp. 533 - 539
• Main Authors: Ren, Megan, Orozco, Anali, Shao, Kang, Albanez, Anaseidy, Ortiz, Jeremy, Cao, Boyang, Wang, Lusheng, Barreda, Lilian, Alvarez, Christian S., Garland, Lisa, Wu, Dongjing, Chung, Charles C., Wang, Jiahui, Frone, Megan, Ralon, Sergio, Argueta, Victor, Orozco, Roberto, Gharzouzi, Eduardo, Dean, Michael
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2021; Springer; Springer Nature B.V
• Subjects: Age; BRCA1 protein; BRCA1 Protein - genetics; BRCA2 protein; BRCA2 Protein - genetics; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Cancer; Cancer research; Diagnosis; Disease susceptibility; Epidemiology; Family medical history; Female; Gene mutations; Genes; Genes, BRCA2; Genetic aspects; Genetic Predisposition to Disease; Genetic screening; Germ Cells; Germ-Line Mutation; Guatemala; Heredity; Humans; Medicine; Medicine & Public Health; Menopause; MSH6 protein; Mutation; Oncology; p53 Protein; Prevention; Tumor proteins; Guatemala; Pathogenic mutation; gene; Hispanic; Health disparities; Latin America; BRCA2 gene; BRCA1 gene
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-021-06305-5

Purpose Mutations in hereditary breast cancer genes play an important role in the risk for cancer. Methods Cancer susceptibility genes were sequenced in 664 unselected breast cancer cases from Guatemala. Variants were annotated with ClinVar and VarSome. Results A total of 73 out of 664 subjects (11%) had a pathogenic variant in a high or moderate penetrance gene. The most frequently mutated genes were BRCA1 (37/664, 5.6%) followed by BRCA2 (15/664, 2.3%), PALB2 (5/664, 0.8%), and TP53 (5/664, 0.8%). Pathogenic variants were also detected in the moderate penetrance genes ATM , BARD1 , CHEK2 , and MSH6 . The high ratio of BRCA1 / BRCA2 mutations is due to two potential founder mutations: BRCA1 c.212  +  1G  >  A splice mutation (15 cases) and BRCA1 c.799delT (9 cases). Cases with pathogenic mutations had a significantly earlier age at diagnosis (45 vs 51 years, P  < 0.001), are more likely to have had diagnosis before menopause, and a higher percentage had a relative with any cancer (51% vs 37%, P  = 0.038) or breast cancer (33% vs 15%, P  < 0.001). Conclusions Hereditary breast cancer mutations were observed among Guatemalan women, and these women are more likely to have early age at diagnosis and family history of cancer. These data suggest the use of genetic testing in breast cancer patients and those at high risk as part of a strategy to reduce breast cancer mortality in Guatemala.