Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population
Abstract Background Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathological condition with increased cancer risk, including breast (BC), ovarian cancer (OC), and others. HBOC pathogenesis is caused mainly by germline pathogenic variants (GPV) in BRCA1 and BRCA2 genes...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-024-01957-9 |
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| author | Dione Aguilar María Lourdes Garza-Rodríguez Carolina Elizabeth Muñiz-Garza Fernando Alcorta Nuñez Cynthia Mayte Villarreal-Garza Oscar Vidal-Gutiérrez Diana Cristina Pérez-Ibave Carlos Horacio Burciaga-Flores |
| author_facet | Dione Aguilar María Lourdes Garza-Rodríguez Carolina Elizabeth Muñiz-Garza Fernando Alcorta Nuñez Cynthia Mayte Villarreal-Garza Oscar Vidal-Gutiérrez Diana Cristina Pérez-Ibave Carlos Horacio Burciaga-Flores |
| author_sort | Dione Aguilar |
| collection | DOAJ |
| description | Abstract Background Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathological condition with increased cancer risk, including breast (BC), ovarian cancer (OC), and others. HBOC pathogenesis is caused mainly by germline pathogenic variants (GPV) in BRCA1 and BRCA2 genes. However, other relevant genes are related to this syndrome diagnosis, prognosis, and treatment, including TP53, PALB2, CHEK2, ATM, etc. This study aimed to identify the prevalence of non-BRCA genes in HBOC patients of Northeast Mexico. Methods This multicentric study included 1285 patients with HBOC diagnosis from four oncologic centers in northeast Mexico from 2016 to 2023. Genomic and clinical data were analyzed based on multi-gene panel results and electronic records of the medical geneticist consultation. For the data analysis of qualitative and quantitative variants, JASP statistical software (version 0.18.1) was used, taking p < 0.05 as a significant result. Results We found that 32.7% of the patients had at least one GPV in non-BRCA genes. The five most frequent non-BRCA genes were CHEK2, PALB2, MUTYH, CDKN2A, and ATM. Among the group of non-BRCA genes, six are involved in the homologous repair pathway (HR), and three are related to DNA damage repair (DDR) pathways. In analyzing GPVs in molecular pathways, both have similar frequencies with no statistical difference for BC. Conclusion Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies. |
| format | Article |
| id | doaj-art-350928f689a9485f9129155b9b2280a7 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-350928f689a9485f9129155b9b2280a72025-01-19T12:44:08ZengBMCBreast Cancer Research1465-542X2025-01-012711910.1186/s13058-024-01957-9Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican populationDione Aguilar0María Lourdes Garza-Rodríguez1Carolina Elizabeth Muñiz-Garza2Fernando Alcorta Nuñez3Cynthia Mayte Villarreal-Garza4Oscar Vidal-Gutiérrez5Diana Cristina Pérez-Ibave6Carlos Horacio Burciaga-Flores7Breast Cancer Center, Hospital Zambrano Hellion TecSaludServicio de Oncología, Centro Universitario Contra el Cáncer (CUCC), Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo LeónFacultad de Medicina, Universidad Autónoma de Nuevo LeónBreast Cancer Center, Hospital Zambrano Hellion TecSaludBreast Cancer Center, Hospital Zambrano Hellion TecSaludServicio de Oncología, Centro Universitario Contra el Cáncer (CUCC), Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo LeónServicio de Oncología, Centro Universitario Contra el Cáncer (CUCC), Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo LeónServicio de Oncología, Centro Universitario Contra el Cáncer (CUCC), Hospital Universitario “Dr. José Eleuterio González”, Universidad Autónoma de Nuevo LeónAbstract Background Hereditary predisposition to breast and ovarian cancer syndrome (HBOC) is a pathological condition with increased cancer risk, including breast (BC), ovarian cancer (OC), and others. HBOC pathogenesis is caused mainly by germline pathogenic variants (GPV) in BRCA1 and BRCA2 genes. However, other relevant genes are related to this syndrome diagnosis, prognosis, and treatment, including TP53, PALB2, CHEK2, ATM, etc. This study aimed to identify the prevalence of non-BRCA genes in HBOC patients of Northeast Mexico. Methods This multicentric study included 1285 patients with HBOC diagnosis from four oncologic centers in northeast Mexico from 2016 to 2023. Genomic and clinical data were analyzed based on multi-gene panel results and electronic records of the medical geneticist consultation. For the data analysis of qualitative and quantitative variants, JASP statistical software (version 0.18.1) was used, taking p < 0.05 as a significant result. Results We found that 32.7% of the patients had at least one GPV in non-BRCA genes. The five most frequent non-BRCA genes were CHEK2, PALB2, MUTYH, CDKN2A, and ATM. Among the group of non-BRCA genes, six are involved in the homologous repair pathway (HR), and three are related to DNA damage repair (DDR) pathways. In analyzing GPVs in molecular pathways, both have similar frequencies with no statistical difference for BC. Conclusion Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies.https://doi.org/10.1186/s13058-024-01957-9Non-BRCABreast cancerOvarian cancerPathogenic germline variantsHereditary cancer |
| spellingShingle | Dione Aguilar María Lourdes Garza-Rodríguez Carolina Elizabeth Muñiz-Garza Fernando Alcorta Nuñez Cynthia Mayte Villarreal-Garza Oscar Vidal-Gutiérrez Diana Cristina Pérez-Ibave Carlos Horacio Burciaga-Flores Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population Breast Cancer Research Non-BRCA Breast cancer Ovarian cancer Pathogenic germline variants Hereditary cancer |
| title | Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population |
| title_full | Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population |
| title_fullStr | Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population |
| title_full_unstemmed | Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population |
| title_short | Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population |
| title_sort | los olvidados non brca variants associated with hereditary breast cancer in mexican population |
| topic | Non-BRCA Breast cancer Ovarian cancer Pathogenic germline variants Hereditary cancer |
| url | https://doi.org/10.1186/s13058-024-01957-9 |
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