CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
Authors
Johnson, N.Maguire, S.
Morra, A.
Kapoor, P. M.
Tomczyk, K.
Jones, M. E.
Schoemaker, M. J.
Gilham, C.
Bolla, M. K.
Wang, Q.
Dennis, J.
Ahearn, T. U.
Andrulis, I. L.
Anton-Culver, H.
Antonenkova, N. N.
Arndt, V.
Aronson, K. J.
Augustinsson, A.
Baynes, C.
Freeman, L. E. B.
Beckmann, M. W.
Benitez, J.
Bermisheva, M.
Blomqvist, C.
Boeckx, B.
Bogdanova, N. V.
Bojesen, S. E.
Brauch, H.
Brenner, H.
Burwinkel, B.
Campa, D.
Canzian, F.
Castelao, J. E.
Chanock, S. J.
Chenevix-Trench, G.
Clarke, C. L.
Conroy, D. M.
Couch, F. J.
Cox, A.
Cross, S. S.
Czene, K.
Dörk, T.
Eliassen, A. H.
Engel, C.
Evans, D. G.
Fasching, P. A.
Figueroa, J.
Floris, G.
Flyger, H.
Gago-Dominguez, M.
Gapstur, S. M.
García-Closas, M.
Gaudet, M. M.
Giles, G. G.
Goldberg, M. S.
González-Neira, A.
Guénel, P.
Hahnen, E.
Haiman, C. A.
Håkansson, N.
Hall, P.
Hamann, U.
Harrington, P. A.
Hart, S. N.
Hooning, M. J.
Hopper, J. L.
Howell, Anthony
Hunter, D. J.
Jager, A.
Jakubowska, A.
John, E. M.
Kaaks, R.
Keeman, R.
Khusnutdinova, E.
Kitahara, C. M.
Kosma, V. M.
Koutros, S.
Kraft, P.
Kristensen, V. N.
Kurian, A. W.
Lambrechts, D.
Le Marchand, L.
Linet, M.
Lubiński, J.
Mannermaa, A.
Manoukian, S.
Margolin, S.
Martens, J. W. M.
Mavroudis, D.
Mayes, R.
Meindl, A.
Milne, R. L.
Neuhausen, S. L.
Nevanlinna, H.
Newman, W. G.
Nielsen, S. F.
Nordestgaard, B. G.
Obi, N.
Olshan, A. F.
Olson, J. E.
Olsson, H.
Orban, E.
Park-Simon, T. W.
Peterlongo, P.
Plaseska-Karanfilska, D.
Pylkäs, K.
Rennert, G.
Rennert, H. S.
Ruddy, K. J.
Saloustros, E.
Sandler, D. P.
Sawyer, E. J.
Schmutzler, R. K.
Scott, C.
Shu, X. O.
Simard, J.
Smichkoska, S.
Sohn, C.
Southey, M. C.
Spinelli, J. J.
Stone, J.
Tamimi, R. M.
Taylor, J. A.
Tollenaar, R.
Tomlinson, I.
Troester, M. A.
Truong, T.
Vachon, C. M.
van Veen, E. M.
Wang, S. S.
Weinberg, C. R.
Wendt, C.
Wildiers, H.
Winqvist, R.
Wolk, A.
Zheng, W.
Ziogas, A.
Dunning, A. M.
Pharoah, P. D. P.
Easton, D. F.
Howie, A. F.
Peto, J.
Dos-Santos-Silva, I.
Swerdlow, A. J.
Chang-Claude, J.
Schmidt, M. K.
Orr, N.
Fletcher, O.
Affiliation
The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.Issue Date
2021
Metadata
Show full item recordAbstract
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).Citation
Johnson N, Maguire S, Morra A, Kapoor PM, Tomczyk K, Jones ME, et al. CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers. Br J Cancer. 2021;124(4):842-54.Journal
British Journal of CancerDOI
10.1038/s41416-020-01185-wPubMed ID
33495599Additional Links
https://dx.doi.org/10.1038/s41416-020-01185-wType
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41416-020-01185-w
Scopus Count
Collections
Related articles
- CYP3A variation, premenopausal estrone levels, and breast cancer risk.
- Authors: Johnson N, Walker K, Gibson LJ, Orr N, Folkerd E, Haynes B, Palles C, Coupland B, Schoemaker M, Jones M, Broderick P, Sawyer E, Kerin M, Tomlinson IP, Zvelebil M, Chilcott-Burns S, Tomczyk K, Simpson G, Williamson J, Hillier SG, Ross G, Houlston RS, Swerdlow A, Ashworth A, Dowsett M, Peto J, Dos Santos Silva I, Fletcher O
- Issue date: 2012 May 2
- CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites.
- Authors: Sood D, Johnson N, Jain P, Siskos AP, Bennett M, Gilham C, Busana MC, Peto J, Dos-Santos-Silva I, Keun HC, Fletcher O
- Issue date: 2017 Jan
- Cytochrome P450 Allele CYP3A7*1C Associates with Adverse Outcomes in Chronic Lymphocytic Leukemia, Breast, and Lung Cancer.
- Authors: Johnson N, De Ieso P, Migliorini G, Orr N, Broderick P, Catovsky D, Matakidou A, Eisen T, Goldsmith C, Dudbridge F, Peto J, Dos-Santos-Silva I, Ashworth A, Ross G, Houlston RS, Fletcher O
- Issue date: 2016 Mar 15
- Reproducibility and validity of radioimmunoassays for urinary hormones and metabolites in pre- and postmenopausal women.
- Authors: Falk RT, Gail MH, Fears TR, Rossi SC, Stanczyk F, Adlercreutz H, Kiura P, Wahala K, Donaldson JL, Vaught JB, Fillmore CM, Hoover RN, Ziegler RG
- Issue date: 1999 Jun
- Ovarian function in premenopausal women affected by breast cancer: the measurement of glucuronoconjugate metabolites of 17 beta-estradiol and progesterone throughout one entire menstrual cycle.
- Authors: Magini A, Pazzagli M, Salerno R, Simonis M, Mustacchi G, Serio M
- Issue date: 1990 Aug 28