Academic Journal
Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants
| العنوان: | Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants |
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| المؤلفون: | Li, Hongyan, Engel, Christoph, de la Hoya, Miguel, Peterlongo, Paolo, Yannoukakos, Drakoulis, Livraghi, Luca, Radice, Paolo, Thomassen, Mads, Hansen, Thomas V.O., Gerdes, Anne Marie, Nielsen, Henriette R., Caputo, Sandrine M., Zambelli, Alberto, Borg, Ake, Solano, Angela, Thomas, Abigail, Parsons, Michael T., Antoniou, Antonis C., Leslie, Goska, Yang, Xin, Chenevix-Trench, Georgia, Caldes, Trinidad, Kwong, Ava, Pedersen, Inge Søkilde, Lautrup, Charlotte K., John, Esther M., Terry, Mary Beth, Hopper, John L., Southey, Melissa C., Andrulis, Irene L., Tischkowitz, Marc, Janavicius, Ramunas, Boonen, Susanne E., Kroeldrup, Lone, Varesco, Liliana, Hamann, Ute, Vega, Ana, Palmero, Edenir I., Garber, Judy, Montagna, Marco, Van Asperen, Christi J., Foretova, Lenka, Greene, Mark H., Selkirk, Tina, Moller, Pal, Toland, Amanda E., Domchek, Susan M., James, Paul A., Thorne, Heather, Eccles, Diana M., Goldgar, David E. |
| سنة النشر: | 2022 |
| المجموعة: | University of Southampton: e-Prints Soton |
| الوصف: | Purpose: Germline genetic testing for BRCA1 and BRCA2 variants has been a part of clinical practice for >2 decades. However, no studies have compared the cancer risks associated with missense pathogenic variants (PVs) with those associated with protein truncating (PTC) variants. Methods: We collected 582 informative pedigrees segregating 1 of 28 missense PVs in BRCA1 and 153 pedigrees segregating 1 of 12 missense PVs in BRCA2. We analyzed 324 pedigrees with PTC variants in BRCA1 and 214 pedigrees with PTC variants in BRCA2. Cancer risks were estimated using modified segregation analysis. Results: Estimated breast cancer risks were markedly lower for women aged >50 years carrying BRCA1 missense PVs than for the women carrying BRCA1 PTC variants (hazard ratio [HR] = 3.9 [2.4-6.2] for PVs vs 12.8 [5.7-28.7] for PTC variants; P =.01), particularly for missense PVs in the BRCA1 C-terminal domain (HR = 2.8 [1.4-5.6]; P =.005). In case of BRCA2, for women aged >50 years, the HR was 3.9 (2.0-7.2) for those heterozygous for missense PVs compared with 7.0 (3.3-14.7) for those harboring PTC variants. BRCA1 p.[Cys64Arg] and BRCA2 p.[Trp2626Cys] were associated with particularly low risks of breast cancer compared with other PVs. Conclusion: These results have important implications for the counseling of at-risk women who harbor missense PVs in the BRCA1/2 genes. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://eprints.soton.ac.uk/454437/1/GIM_2021_Li_Goldgar.pdf; Li, Hongyan, Engel, Christoph, de la Hoya, Miguel, Peterlongo, Paolo, Yannoukakos, Drakoulis, Livraghi, Luca, Eccles, Diana M. and Goldgar, David E. , ENIGMA Consortium and CIMBA Consortium (2022) Risks of breast and ovarian cancer for women harboring pathogenic missense variants in BRCA1 and BRCA2 compared with those harboring protein truncating variants. Genetics in Medicine, 24 (1), 119-129. (doi:10.1016/j.gim.2021.08.016 ). |
| الاتاحة: | https://eprints.soton.ac.uk/454437/ https://eprints.soton.ac.uk/454437/1/GIM_2021_Li_Goldgar.pdf |
| Rights: | cc_by_nc_nd_4 |
| رقم الانضمام: | edsbas.A56CA1C7 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |