Maryam Bagherzadeh1,2, Agata Szymiczek1, Talia Donenberg3, Raleigh Butler4, Judith Hurley3, Steven A Narod1,2,5, Mohammad R Akbari6,7,8. 1. Women's College Research Institute, University of Toronto, Toronto, Canada. 2. Institite of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada. 3. Sylvester Comprehensive Cancer Center, University of Miami, Miami, USA. 4. Princess Margaret Hospital, Nassau, Bahamas. 5. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. 6. Institite of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Canada. mohammad.akbari@utoronto.ca. 7. Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. mohammad.akbari@utoronto.ca. 8. Women's College Research Institute, University of Toronto, 76 Grenville Street, Room 6421, Toronto, ON, M5S 1B2, Canada. mohammad.akbari@utoronto.ca.
Abstract
PURPOSE: RAD51C is known as an ovarian cancer gene; however, its role in breast cancer susceptibility is less clear. As part of a larger study, we assessed the role of germline RAD51C mutations in breast cancer development. METHODS: We studied 387 unselected, BRCA1- and BRCA2-negative, Bahamian breast cancer cases and 653 controls to search for novel genetic associations with breast cancer development. During the first phase of the study, whole exome sequencing was utilized in 96 cases to identify an association between novel genes and breast cancer susceptibility. In the second phase of the study, targeted gene sequencing was utilized in the entirety of the cases and controls to identify an association between novel genetic mutations and breast cancer development. RESULTS: A RAD51C mutation was found in five breast cancer cases and in no control (5/387 versus 0/653; p = 0.007). None of the mutation-positive cases reported a family history of ovarian cancer. CONCLUSIONS: These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.
PURPOSE: RAD51C is known as an ovarian cancer gene; however, its role in breast cancer susceptibility is less clear. As part of a larger study, we assessed the role of germline RAD51C mutations in breast cancer development. METHODS: We studied 387 unselected, BRCA1- and BRCA2-negative, Bahamian breast cancer cases and 653 controls to search for novel genetic associations with breast cancer development. During the first phase of the study, whole exome sequencing was utilized in 96 cases to identify an association between novel genes and breast cancer susceptibility. In the second phase of the study, targeted gene sequencing was utilized in the entirety of the cases and controls to identify an association between novel genetic mutations and breast cancer development. RESULTS: A RAD51C mutation was found in five breast cancer cases and in no control (5/387 versus 0/653; p = 0.007). None of the mutation-positive cases reported a family history of ovarian cancer. CONCLUSIONS: These data support increasing evidence that RAD51C mutations contribute to breast cancer susceptibility, although the impact may vary substantially from country to country.
Entities:
Keywords:
Breast cancer genetics; Gene discovery; Hereditary breast cancer; RAD51C mutations
Authors: Na Li; Simone McInerny; Magnus Zethoven; Dane Cheasley; Belle W X Lim; Simone M Rowley; Lisa Devereux; Norah Grewal; Somayeh Ahmadloo; David Byrne; Jue Er Amanda Lee; Jason Li; Stephen B Fox; Thomas John; Yoland Antill; Kylie L Gorringe; Paul A James; Ian G Campbell Journal: J Natl Cancer Inst Date: 2019-12-01 Impact factor: 13.506
Authors: Sophia H L George; Talia Donenberg; Cheryl Alexis; Vincent DeGennaro; Hedda Dyer; Sook Yin; Jameel Ali; Raleigh Butler; Sheray N Chin; DuVaughn Curling; Dwight Lowe; John Lunn; Theodore Turnquest; Gilian Wharfe; Danielle Cerbon; Priscila Barreto-Coelho; Matthew P Schlumbrecht; Mohammad R Akbari; Steven A Narod; Judith E Hurley Journal: JAMA Netw Open Date: 2021-03-01