- Title
- Genome-wide association study of germline variants and breast cancer-specific mortality
- Creator
- Escala-Garcia, Maria; Figueroa, J; Flesch-Janys, D; Flyger, H; Gabrielson, M; Gago-Dominguez, M; Galle, E; Gapstur, SM; García-Closas, M; García-Sáenz, JA; Gaudet, MM; George, A; Georgoulias, V; Giles, GG; Glendon, G; Goldgar, DE; González-Neira, A; Alnæs, GIG; Grip, M; Guénel, P; Haeberle, L; Hahnen, E; Haiman, CA; Håkansson, N; Hall, P; Hamann, U; Hankinson, S; Harkness, EF; Harrington, PA; Hart, SN; Hartikainen, JM; Hein, A; Hillemanns, P; Hiller, L; Holleczek, B; Hollestelle, A; Guo, Qi; Abraham, Jean; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Auer, Paul L.; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Bermisheva, Marina; Bernstein, Leslie; Dörk, Thilo; Scott, Rodney J.; Boeckx, B; Bojesen, SE; Bonanni, B; Børresen-Dale, AL; Brauch, H; Brenner, H; Brentnall, A; Brinton, L; Broberg, P; Canisius, Sander; Brock, IW; Brucker, SY; Burwinkel, B; Caldas, C; Caldés, T; Campa, D; Canzian, F; Carracedo, A; Carter, BD; Castelao, JE; Keeman, Renske; Chang-Claude, J; Chanock, SJ; Chenevix-Trench, G; Cheng, TYD; Chin, SF; Clarke, CL; Cordina-Duverger, E; Couch, FJ; Cox, DG; Cox, A; Dennis, Joe; Cross, SS; Czene, K; Daly, MB; Devilee, P; Dunn, JA; Dunning, AM; Durcan, L; Dwek, M; Earl, HM; Ekici, AB; Beesley, Jonathan; Eliassen, AH; Ellberg, C; Engel, C; Eriksson, M; Scott , RJ; Lecarpentier, Julie; Bolla, Manjeet K.; Wang, Qin
- Relation
- British Journal of Cancer Vol. 120, Issue 6, p. 647-657
- Publisher Link
- http://dx.doi.org/10.1038/s41416-019-0393-x
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2019
- Description
- 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.
- Subject
- germline; breast cancer; women; ancestry; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1467287
- Identifier
- uon:47795
- Identifier
- ISSN:0007-0920
- Language
- eng
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