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. 2021 Sep;189(2):533-539.
doi: 10.1007/s10549-021-06305-5. Epub 2021 Jul 1.

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

Megan Ren #  1 , Anali Orozco #  2 , Kang Shao #  3 , Anaseidy Albanez  2 , Jeremy Ortiz  2 , Boyang Cao  3 , Lusheng Wang  4   5 , Lilian Barreda  6 , Christian S Alvarez  1 , Lisa Garland  7 , Dongjing Wu  7 , Charles C Chung  7   8 , Jiahui Wang  7 , Megan Frone  1 , Sergio Ralon  6 , Victor Argueta  6 , Roberto Orozco  9 , Eduardo Gharzouzi  10 , Michael Dean  11
Affiliations

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

Megan Ren et al. Breast Cancer Res Treat. 2021 Sep.

Erratum in

Abstract

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.

Keywords: BRCA1 gene; BRCA2 gene; Health disparities; Hispanic; Latin America; Pathogenic mutation.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Pathogenic mutations in high and moderate penetrance genes. A Shown is the percentage of all pathogenic mutations in moderate and high penetrance genes, by gene or B by recurrent mutation. C The groupings of patients are shown by variant type
See this image and copyright information in PMC

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