Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing
| Autor: | Margaret Akinhanmi, Brigette Tippin Davis, Priyanka Sharma, Drakoulis Yannoukakos, Eric C. Polley, Raymond Moore, David E. Goldgar, Peter A. Fasching, Jill S. Dolinsky, Abigail Thomas, Heli Nevanlinna, Judy Garber, Diana Eccles, Hiltrud Brauch, Andrew K. Godwin, Bing Jian Feng, Holly LaDuca, Angela Cox, Song Yao, Hermela Shimelis, Jie Na, Florentia Fostira, Steven N. Hart, Fergus J. Couch, Tina Pesaran, Amanda Ewart-Toland, Chunling Hu, Jenna Lilyquist, Irene Konstantopoulou |
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| Přispěvatelé: | Doctoral Programme in Biomedicine, Department of Obstetrics and Gynecology, Clinicum |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research Triple Negative Breast Neoplasms PHENOTYPE 0302 clinical medicine Gene Frequency Risk Factors Odds Ratio CONFER SUSCEPTIBILITY Age of Onset Triple-negative breast cancer medicine.diagnostic_test WOMEN Articles Middle Aged 3. Good health 030220 oncology & carcinogenesis SURVIVAL Female Adult medicine.medical_specialty PALB2 3122 Cancers OVARIAN-CANCER 03 medical and health sciences Young Adult Breast cancer Internal medicine medicine Biomarkers Tumor Humans Genetic Predisposition to Disease Genetic Testing INHERITED MUTATIONS Alleles Genetic Association Studies Genetic testing REPAIR Cancer prevention business.industry Case-control study Cancer Odds ratio medicine.disease 030104 developmental biology Case-Control Studies Mutation business Genome-Wide Association Study |
| Zdroj: | JNCI Journal of the National Cancer Institute |
| ISSN: | 0027-8874 |
| Popis: | Background\ud Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor–negative, progesterone receptor–negative, human epidermal growth factor receptor–negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC.\ud \ud Methods\ud Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls.\ud \ud Results\ud Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants.\ud \ud Conclusions\ud Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies. |
| Databáze: | OpenAIRE |
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