- Title
- CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
- Creator
- Johnson, Nichola; Maguire, Sarah; Dennis, Joe; Ahearn, Thomas U.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Augustinsson, Annelie; Baynes, Caroline; Freeman, Laura E. Beane; Morra, Anna; Beckmann, MW; Benitez, J; Bermisheva, M; Blomqvist, C; Boeckx, B; Bogdanova, NV; Bojesen, SE; Brauch, H; Brenner, H; Burwinkel, B; Kapoor, Pooja Middha; Campa, D; Canzian, F; Castelao, JE; Chanock, SJ; Chenevix-Trench, G; Clarke, CL; Børresen-Dale, AL; Alnæs, GIG; Sahlberg, KK; Ottestad, L; Tomczyk, Katarzyna; Kåresen, R; Schlichting, E; Holmen, MM; Sauer, T; Haakensen, V; Engebråten, O; Naume, B; Fosså, A; Kiserud, CE; Reinertsen, KV; Jones, Michael E.; Helland, Å; Riis, M; Geisler, J; Conroy, DM; Couch, FJ; Cox, A; Cross, SS; Czene, K; Dörk, T; Eliassen, AH; Schoemaker, Minouk J.; Engel, C; Evans, DG; Fasching, PA; Figueroa, J; Floris, G; Flyger, H; Gago-Dominguez, M; Gapstur, SM; García-Closas, M; Gaudet, MM; Gilham, Clare; Giles, GG; Goldberg, MS; González-Neira, A; Bowtell, DDL; deFazio, A; Webb, PM; Guénel, P; Hahnen, E; Haiman, CA; Håkansson, N; Bolla, Manjeet K.; Hall, P; Hamann, U; Harrington, PA; Hart, SN; Hooning, MJ; Hopper, JL; Howell, A; Hunter, DJ; Clarke, C; Marsh, D; Wang, Qin; Scott, Rodney; Baxter, R; Yip, D; Carpenter, J; Davis, A; Pathmanathan, N; Simpson, P; Graham, D; Sachchithananthan, M; Amor, D
- Relation
- British Journal of Cancer Vol. 124, Issue 4, p. 842-854
- Publisher Link
- http://dx.doi.org/10.1038/s41416-020-01185-w
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2021
- Description
- Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
- Subject
- breast; estrone; progesterone; receptor; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1474586
- Identifier
- uon:49307
- Identifier
- ISSN:0007-0920
- Language
- eng
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