TY - JOUR
T1 - A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
AU - GEMO Study Collaborators
AU - EMBRACE Collaborators
AU - kConFab Investigators
AU - HEBON Investigators
AU - ABCTB Investigators
AU - Coignard, Juliette
AU - Lush, Michael
AU - Beesley, Jonathan
AU - O’Mara, Tracy A.
AU - Dennis, Joe
AU - Tyrer, Jonathan P.
AU - Barnes, Daniel R.
AU - McGuffog, Lesley
AU - Leslie, Goska
AU - Bolla, Manjeet K.
AU - Adank, Muriel A.
AU - Agata, Simona
AU - Ahearn, Thomas
AU - Aittomäki, Kristiina
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Arnold, Norbert
AU - Aronson, Kristan J.
AU - Arun, Banu K.
AU - Augustinsson, Annelie
AU - Azzollini, Jacopo
AU - Barrowdale, Daniel
AU - Baynes, Caroline
AU - Becher, Heko
AU - Bermisheva, Marina
AU - Bernstein, Leslie
AU - Białkowska, Katarzyna
AU - Blomqvist, Carl
AU - Bojesen, Stig E.
AU - Bonanni, Bernardo
AU - Borg, Ake
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Burwinkel, Barbara
AU - Buys, Saundra S.
AU - Caldés, Trinidad
AU - Caligo, Maria A.
AU - Campa, Daniele
AU - Carter, Brian D.
AU - Castelao, Jose E.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Chung, Wendy K.
AU - Claes, Kathleen B.M.
AU - Clarke, Christine L.
AU - Bertrand, Ophélie
AU - Caputo, Sandrine
AU - Dupré, Anaïs
AU - Torres, Diana
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
AB - Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
UR - https://www.scopus.com/pages/publications/85101270098
U2 - 10.1038/s41467-020-20496-3
DO - 10.1038/s41467-020-20496-3
M3 - Article
C2 - 33990587
AN - SCOPUS:85101270098
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1078
ER -
SDG 3 Good Health and Well-being