دورية أكاديمية
Germline breast cancer susceptibility genes, tumor characteristics, and survival.
| العنوان: | Germline breast cancer susceptibility genes, tumor characteristics, and survival. |
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| المؤلفون: | Ho, Peh Joo, Khng, Alexis J, Loh, Hui Wen, Ho, Weang-Kee, Yip, Cheng Har, Mohd-Taib, Nur Aishah, Tan, Veronique Kiak Mien, Tan, Benita Kiat-Tee, Tan, Su-Ming, Tan, Ern Yu, Lim, Swee Ho, Jamaris, Suniza, Sim, Yirong, Wong, Fuh Yong, Ngeow, Joanne, Lim, Elaine Hsuen, Tai, Mei Chee, Wijaya, Eldarina Azfar, Lee, Soo Chin, Chan, Ching Wan, Buhari, Shaik Ahmad, Chan, Patrick MY, Chen, Juliana JC, Seah, Jaime Chin Mui, Lee, Wai Peng, Mok, Chi Wei, Lim, Geok Hoon, Woo, Evan, Kim, Sung-Won, Lee, Jong Won, Lee, Min Hyuk, Park, Sue K, Dunning, Alison M, Easton, Douglas F, Schmidt, Marjanka K, Teo, Soo-Hwang, Li, Jingmei, Hartman, Mikael |
| المصدر: | essn: 1756-994X ; nlmid: 101475844 |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1186/s13073-021-00978-9 Genome Med |
| سنة النشر: | 2022 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Breast cancer, Overall survival, Protein-truncating variants, BRCA1 Protein, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genetic Testing, Germ Cells, Germ-Line Mutation, Humans, Odds Ratio |
| الوصف: | BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/332508Test |
| DOI: | 10.17863/CAM.79958 |
| الإتاحة: | https://doi.org/10.17863/CAM.79958Test https://www.repository.cam.ac.uk/handle/1810/332508Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.3E8041EB |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.79958 |
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