التفاصيل البيبلوغرافية
| العنوان: |
Enhancing the BOADICEA cancer risk prediction model to incorporate new data on RAD51C, RAD51D, BARD1updates to tumour pathology and cancer incidence |
| المؤلفون: |
Lee, Andrew, Mavaddat, Nasim, Cunningham, Alex, Carver, Tim, Ficorella, Lorenzo, Archer, Stephanie, Walter, Fiona M, Tischkowitz, Marc, Roberts, Jonathan, Usher-Smith, Juliet, Simard, Jacques, Schmidt, Marjanka K, Devilee, Peter, Zadnik, Vesna, Jürgens, Hannes, Mouret-Fourme, Emmanuelle, De Pauw, Antoine, Rookus, Matti, Mooij, Thea M, Pharoah, Paul PD, Easton, Douglas F, Antoniou, Antonis C |
| المساهمون: |
the Quebec Breast Cancer Foundation, the CHU de Quebec, Government of Canada, Canadian Institutes of Health Research, Cancer Research UK, European Union, NIHR Cambridge Biomedical Research Centre |
| المصدر: |
Journal of Medical Genetics ; volume 59, issue 12, page 1206-1218 ; ISSN 0022-2593 1468-6244 |
| بيانات النشر: |
BMJ |
| سنة النشر: |
2022 |
| الوصف: |
Background BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool ( www.canrisk.org ) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. Methods BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1 , RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. Results BARD1 , RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%–44% of these carriers would be reclassified to the near-population and 15%–22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of <5%, 5%–10% and >10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. Conclusions These extensions will allow for better personalised risks for BARD1 , RAD51C , RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1136/jmedgenet-2022-108471 |
| الإتاحة: |
https://doi.org/10.1136/jmedgenet-2022-108471Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.61300A5B |
| قاعدة البيانات: |
BASE |
