TY - JOUR
T1 - Two truncating variants in FANCC and breast cancer risk
AU - ABCTB Investigators
AU - NBCS Collaborators
AU - Dörk, Thilo
AU - Peterlongo, Paolo
AU - Mannermaa, Arto
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Dennis, Joe
AU - Ahearn, Thomas
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Aronson, Kristan J.
AU - Augustinsson, Annelie
AU - Freeman, Laura E.Beane
AU - Beckmann, Matthias W.
AU - Beeghly-Fadiel, Alicia
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Burwinkel, Barbara
AU - Canzian, Federico
AU - Chan, Tsun L.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Choi, Ji Yeob
AU - Christiansen, Hans
AU - Clarke, Christine L.
AU - Couch, Fergus J.
AU - Czene, Kamila
AU - Daly, Mary B.
AU - dos-Santos-Silva, Isabel
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Ekici, Arif B.
AU - Eriksson, Mikael
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Fritschi, Lin
AU - Gabrielson, Marike
AU - Gago-Dominguez, Manuela
AU - Gao, Chi
AU - Gapstur, Susan M.
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Torres, Diana
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
AB - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
UR - https://www.scopus.com/pages/publications/85071631153
U2 - 10.1038/s41598-019-48804-y
DO - 10.1038/s41598-019-48804-y
M3 - Article
C2 - 31467304
AN - SCOPUS:85071631153
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12524
ER -
ODS 3: Salud y bienestar