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    CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

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    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.
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    Affiliation
    The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, UK.
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    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 Cancer
    URI
    http://hdl.handle.net/10541/623785
    DOI
    10.1038/s41416-020-01185-w
    PubMed ID
    33495599
    Additional Links
    https://dx.doi.org/10.1038/s41416-020-01185-w
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41416-020-01185-w
    Scopus Count
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    All Christie Publications

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