Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls
Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown.Methods: We performed sequencing on a popula...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1248492/full |
| _version_ | 1797681910239985664 |
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| author | Maria Zanti Maria A. Loizidou Denise G. O’Mahony Leila Dorling Joe Dennis Peter Devilee Peter Devilee Douglas F. Easton Douglas F. Easton Mihalis I. Panayiotidis Andreas Hadjisavvas Kyriaki Michailidou Kyriaki Michailidou |
| author_facet | Maria Zanti Maria A. Loizidou Denise G. O’Mahony Leila Dorling Joe Dennis Peter Devilee Peter Devilee Douglas F. Easton Douglas F. Easton Mihalis I. Panayiotidis Andreas Hadjisavvas Kyriaki Michailidou Kyriaki Michailidou |
| author_sort | Maria Zanti |
| collection | DOAJ |
| description | Introduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown.Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants.Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes.Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical implications for women who undergo genetic testing and be pivotal for a substantial proportion of breast cancer patients in Cyprus. |
| first_indexed | 2024-03-11T23:51:50Z |
| format | Article |
| id | doaj.art-1ed6479f76b24713ac02555701450926 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T23:51:50Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1ed6479f76b24713ac025557014509262023-09-19T06:44:54ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.12484921248492Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controlsMaria Zanti0Maria A. Loizidou1Denise G. O’Mahony2Leila Dorling3Joe Dennis4Peter Devilee5Peter Devilee6Douglas F. Easton7Douglas F. Easton8Mihalis I. Panayiotidis9Andreas Hadjisavvas10Kyriaki Michailidou11Kyriaki Michailidou12Biostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusDepartment of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusBiostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United KingdomDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United KingdomDepartment of Human Genetics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Pathology, Leiden University Medical Center, Leiden, NetherlandsDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United KingdomDepartment of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United KingdomDepartment of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusDepartment of Cancer Genetics, Therapeutics and Ultrastructural Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusBiostatistics Unit, The Cyprus Institute of Neurology and Genetics, Nicosia, CyprusDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, United KingdomIntroduction: It is estimated that around 5% of breast cancer cases carry pathogenic variants in established breast cancer susceptibility genes. However, the underlying prevalence and gene-specific population risk estimates in Cyprus are currently unknown.Methods: We performed sequencing on a population-based case-control study of 990 breast cancer cases and 1094 controls from Cyprus using the BRIDGES sequencing panel. Analyses were conducted separately for protein-truncating and rare missense variants.Results: Protein-truncating variants in established breast cancer susceptibility genes were detected in 3.54% of cases and 0.37% of controls. Protein-truncating variants in BRCA2 and ATM were associated with a high risk of breast cancer, whereas PTVs in BRCA1 and PALB2 were associated with a high risk of estrogen receptor (ER)-negative disease. Among participants with a family history of breast cancer, PTVs in ATM, BRCA2, BRCA1, PALB2 and RAD50 were associated with an increased risk of breast cancer. Furthermore, an additional 19.70% of cases and 17.18% of controls had at least one rare missense variant in established breast cancer susceptibility genes. For BRCA1 and PALB2, rare missense variants were associated with an increased risk of overall and triple-negative breast cancer, respectively. Rare missense variants in BRCA1, ATM, CHEK2 and PALB2 domains, were associated with increased risk of disease subtypes.Conclusion: This study provides population-based prevalence and gene-specific risk estimates for protein-truncating and rare missense variants. These results may have important clinical implications for women who undergo genetic testing and be pivotal for a substantial proportion of breast cancer patients in Cyprus.https://www.frontiersin.org/articles/10.3389/fgene.2023.1248492/fullbreast cancer susceptibilitypanel sequencingMASTOS studycase-controlnext-generation sequencing |
| spellingShingle | Maria Zanti Maria A. Loizidou Denise G. O’Mahony Leila Dorling Joe Dennis Peter Devilee Peter Devilee Douglas F. Easton Douglas F. Easton Mihalis I. Panayiotidis Andreas Hadjisavvas Kyriaki Michailidou Kyriaki Michailidou Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls Frontiers in Genetics breast cancer susceptibility panel sequencing MASTOS study case-control next-generation sequencing |
| title | Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls |
| title_full | Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls |
| title_fullStr | Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls |
| title_full_unstemmed | Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls |
| title_short | Multi-gene panel testing and association analysis in Cypriot breast cancer cases and controls |
| title_sort | multi gene panel testing and association analysis in cypriot breast cancer cases and controls |
| topic | breast cancer susceptibility panel sequencing MASTOS study case-control next-generation sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1248492/full |
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