التفاصيل البيبلوغرافية
| العنوان: |
Comprehensive epithelial tubo-ovarian cancer risk prediction model incorporating genetic and epidemiological risk factors |
| المؤلفون: |
Lee, Andrew, Yang, Xin, Tyrer, Jonathan, Gentry-Maharaj, Aleksandra, Ryan, Andy, Mavaddat, Nasim, Cunningham, Alex P, Carver, Tim, Archer, Stephanie, Leslie, Goska, Kalsi, Jatinder, Gaba, Faiza, Manchanda, Ranjit, Gayther, Simon, Ramus, Susan J, Walter, Fiona M, Tischkowitz, Marc, Jacobs, Ian, Menon, Usha, Easton, Douglas F, Pharoah, Paul, Antoniou, Antonis C |
| المساهمون: |
Government of Canada, Medical Research Council, Department of Health, Ontario Research Fund, Canadian Institutes of Health Research, Ministère de l'Économie, de la Science et de l'Innovation - Québec, CHU de Quebec Foundation, FP7 Health, Cancer Research UK, National Institute for Health Research, Fondation du cancer du sein du Québec, The Eve Appeal |
| المصدر: |
Journal of Medical Genetics ; volume 59, issue 7, page 632-643 ; ISSN 0022-2593 1468-6244 |
| بيانات النشر: |
BMJ |
| سنة النشر: |
2021 |
| الوصف: |
Background Epithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention. Methods We developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1 , BRCA2 , RAD51C , RAD51D and BRIP1 , a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively. Results Based on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%–10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk. Conclusion This multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool ( www.canrisk.org ). |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1136/jmedgenet-2021-107904 |
| الإتاحة: |
https://doi.org/10.1136/jmedgenet-2021-107904Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.802FECF5 |
| قاعدة البيانات: |
BASE |
