TY - JOUR
T1 - Genome-wide association study of germline variants and breast cancer-specific mortality
AU - NBCS Collaborators
AU - Escala-Garcia, Maria
AU - Guo, Qi
AU - Dörk, Thilo
AU - Canisius, Sander
AU - Keeman, Renske
AU - Dennis, Joe
AU - Beesley, Jonathan
AU - Lecarpentier, Julie
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Abraham, Jean
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Auer, Paul L.
AU - Beckmann, Matthias W.
AU - Behrens, Sabine
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Bernstein, Leslie
AU - Blomqvist, Carl
AU - Boeckx, Bram
AU - Bojesen, Stig E.
AU - Bonanni, Bernardo
AU - Børresen-Dale, Anne Lise
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Brentnall, Adam
AU - Brinton, Louise
AU - Broberg, Per
AU - Brock, Ian W.
AU - Brucker, Sara Y.
AU - Burwinkel, Barbara
AU - Caldas, Carlos
AU - Caldés, Trinidad
AU - Campa, Daniele
AU - Canzian, Federico
AU - Carracedo, Angel
AU - Carter, Brian D.
AU - Castelao, Jose E.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Chenevix-Trench, Georgia
AU - Cheng, Ting Yuan David
AU - Chin, Suet Feung
AU - Clarke, Christine L.
AU - Cordina-Duverger, Emilie
AU - Couch, Fergus J.
AU - Cox, David G.
AU - Torres, Diana
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/3/19
Y1 - 2019/3/19
N2 - Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10 −8 . For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10 −7 , hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10 −7 , HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
AB - Background: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results: We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10 −8 . For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10 −7 , hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2. For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10 −7 , HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions: We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.
UR - https://www.scopus.com/pages/publications/85061925826
U2 - 10.1038/s41416-019-0393-x
DO - 10.1038/s41416-019-0393-x
M3 - Article
C2 - 30787463
AN - SCOPUS:85061925826
SN - 0007-0920
VL - 120
SP - 647
EP - 657
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 6
ER -
ODS 3: Salud y bienestar