Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE
Abstract Background Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM),...
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2025-05-01
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| Online Access: | https://doi.org/10.1186/s13058-025-02030-9 |
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| author | Nasim Mavaddat Debra Frost Emily Zhao Daniel R. Barnes Munaza Ahmed Julian Barwell Angela F. Brady Paul Brennan Hector Conti Jackie Cook Harriet Copeland Rosemarie Davidson Alan Donaldson Emma Douglas David Gallagher Rachel Hart Louise Izatt Zoe Kemp Fiona Lalloo Zosia Miedzybrodzka Patrick J. Morrison Jennie E. Murray Alex Murray Hannah Musgrave Claire Searle Lucy Side Katie Snape Vishakha Tripathi Lisa Walker Stephanie Archer D. Gareth Evans Marc Tischkowitz Antonis C. Antoniou Douglas F. Easton |
| author_facet | Nasim Mavaddat Debra Frost Emily Zhao Daniel R. Barnes Munaza Ahmed Julian Barwell Angela F. Brady Paul Brennan Hector Conti Jackie Cook Harriet Copeland Rosemarie Davidson Alan Donaldson Emma Douglas David Gallagher Rachel Hart Louise Izatt Zoe Kemp Fiona Lalloo Zosia Miedzybrodzka Patrick J. Morrison Jennie E. Murray Alex Murray Hannah Musgrave Claire Searle Lucy Side Katie Snape Vishakha Tripathi Lisa Walker Stephanie Archer D. Gareth Evans Marc Tischkowitz Antonis C. Antoniou Douglas F. Easton |
| author_sort | Nasim Mavaddat |
| collection | DOAJ |
| description | Abstract Background Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited. Methods We used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status. Results No statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5 cm difference, p = 0.003). Conclusion Information on the distribution of cancer risk factors in PV carriers is needed for incorporating these factors into multifactorial cancer risk prediction algorithms. Contrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. We highlight methodological considerations and data limitations inherent in studies aiming to address this question. |
| format | Article |
| id | doaj-art-915836c9e2fe45f6a1dfbc638128e99c |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| series | Breast Cancer Research |
| spelling | doaj-art-915836c9e2fe45f6a1dfbc638128e99c2025-08-20T03:47:45ZengBMCBreast Cancer Research1465-542X2025-05-0127111210.1186/s13058-025-02030-9Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACENasim Mavaddat0Debra Frost1Emily Zhao2Daniel R. Barnes3Munaza Ahmed4Julian Barwell5Angela F. Brady6Paul Brennan7Hector Conti8Jackie Cook9Harriet Copeland10Rosemarie Davidson11Alan Donaldson12Emma Douglas13David Gallagher14Rachel Hart15Louise Izatt16Zoe Kemp17Fiona Lalloo18Zosia Miedzybrodzka19Patrick J. Morrison20Jennie E. Murray21Alex Murray22Hannah Musgrave23Claire Searle24Lucy Side25Katie Snape26Vishakha Tripathi27Lisa Walker28Stephanie Archer29D. Gareth Evans30Marc Tischkowitz31Antonis C. Antoniou32Douglas F. Easton33Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeNorth East Thames Regional Clinical Genetics Service, Great Ormond Street HospitalLeicestershire, Northamptonshire and Rutland Clinical Genetics Service, University Hospitals of Leicester NHS TrustNorth West Thames Regional Genetics Service, London North West University Healthcare NHS TrustNorthern Genetics Service, Newcastle Upon Tyne NHS Foundation TrustAll Wales Medical Genomics Services, Wrexham Maelor HospitalSheffield Clinical Genetics Service, Sheffield Children’s HospitalDepartment Clinical Genetics, Royal Devon University Healthcare NHS Foundation TrustDepartment of Clinical Genetics, South Glasgow University HospitalsClinical Genetics Department, St Michael’s HospitalWest Midlands Regional Clinical Genetics Service, Birmingham Women’s HospitalTrinity St Jame’s Cancer Institute, Cancer Genetics ServiceLiverpool Women’s Hospital Cheshire and Merseyside Genetics, Liverpool Women’s NHS Foundation TrustClinical Genetics, Guy’s and St. Thomas’ NHS Foundation TrustRoyal Marsden Hospital, NHS TrustClinical Genetics Service, Manchester Centre for Genomic Medicine, Manchester University Hospitals Foundation TrustNHS Grampian, North of Scotland Regional Genetics ServiceBelfast Health and Social Care Trust, Clinical Genetics ServiceSouth East Scotland Clinical Genetics Service, Western General HospitalAll Wales Medical Genomics Service, Wales Genomic Health CentreLeeds Genomic Medicine Service, Leeds Teaching Hospitals NHS TrustDepartment of Clinical Genetics, Nottingham University Hospitals NHS TrustUniversity Hospital Southampton NHS Trust and Princess Anne HospitalMedical Genetics Unit, St George’s, University of LondonClinical Genetics, Guy’s and St. Thomas’ NHS Foundation TrustOxford Centre for Genomic Medicine, Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation TrustDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeGenomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution, Infection and Genomic Science, University of Manchester, Manchester University Hospitals NHS Foundation TrustDepartment of Genomic Medicine, Cambridge Biomedical Research Centre, National Institute for Health Research, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeDepartment of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of CambridgeAbstract Background Carriers of germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are at higher risk of developing breast and ovarian cancer than the general population. It is unclear if these PVs influence other breast or ovarian cancer risk factors, including age at menopause (ANM), age at menarche (AAM), menstrual cycle length, BMI or height. There is a biological rationale for associations between BRCA1 and BRCA2 PVs and reproductive traits, for example involving DNA damage and repair mechanisms. The evidence for or against such associations is limited. Methods We used data on 3,046 BRCA1 and 3,264 BRCA2 PV carriers, and 2,857 non-carrier female relatives of PV carriers from the Epidemiological Study of Familial Breast Cancer (EMBRACE). Associations between ANM and PV carrier status was evaluated using linear regression models allowing for censoring. AAM, menstrual cycle length, BMI, and height in carriers and non-carriers were compared using linear and multinomial logistic regression. Analyses were adjusted for potential confounders, and weighted analyses carried out to account for non-random sampling with respect to cancer status. Results No statistically significant difference in ANM between carriers and non-carriers was observed in analyses accounting for censoring. Linear regression effect sizes for ANM were -0.002 (95%CI: -0.401, 0.397) and -0.172 (95%CI: -0.531, 0.188), for BRCA1 and BRCA2 PV carriers respectively, compared with non-carrier women. The distributions of AAM, menstrual cycle length and BMI were similar between PV carriers and non-carriers, but BRCA1 PV carriers were slightly taller on average than non-carriers (0.5 cm difference, p = 0.003). Conclusion Information on the distribution of cancer risk factors in PV carriers is needed for incorporating these factors into multifactorial cancer risk prediction algorithms. Contrary to previous reports, we found no evidence that BRCA1 or BRCA2 PV are associated with hormonal or anthropometric factors, except for a weak association with height. We highlight methodological considerations and data limitations inherent in studies aiming to address this question.https://doi.org/10.1186/s13058-025-02030-9BRCA1BRCA2MenopauseMenarcheHeightBody mass index |
| spellingShingle | Nasim Mavaddat Debra Frost Emily Zhao Daniel R. Barnes Munaza Ahmed Julian Barwell Angela F. Brady Paul Brennan Hector Conti Jackie Cook Harriet Copeland Rosemarie Davidson Alan Donaldson Emma Douglas David Gallagher Rachel Hart Louise Izatt Zoe Kemp Fiona Lalloo Zosia Miedzybrodzka Patrick J. Morrison Jennie E. Murray Alex Murray Hannah Musgrave Claire Searle Lucy Side Katie Snape Vishakha Tripathi Lisa Walker Stephanie Archer D. Gareth Evans Marc Tischkowitz Antonis C. Antoniou Douglas F. Easton Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE Breast Cancer Research BRCA1 BRCA2 Menopause Menarche Height Body mass index |
| title | Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE |
| title_full | Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE |
| title_fullStr | Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE |
| title_full_unstemmed | Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE |
| title_short | Distribution of age at natural menopause, age at menarche, menstrual cycle length, height and BMI in BRCA1 and BRCA2 pathogenic variant carriers and non-carriers: results from EMBRACE |
| title_sort | distribution of age at natural menopause age at menarche menstrual cycle length height and bmi in brca1 and brca2 pathogenic variant carriers and non carriers results from embrace |
| topic | BRCA1 BRCA2 Menopause Menarche Height Body mass index |
| url | https://doi.org/10.1186/s13058-025-02030-9 |
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