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CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
Johnson, N. ; Maguire, S. ; Morra, A. ; Kapoor, P. M. (First author)DKFZ* ; 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.DKFZ* ; 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.DKFZ* ; Brenner, H.DKFZ* ; Burwinkel, B.DKFZ* ; Campa, D. ; Canzian, F.DKFZ* ; Castelao, J. E. ; Chanock, S. J. ; Chenevix-Trench, G. ; Clarke, C. L. ; NBCS Collaborators (Collaboration Author) ; 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. ; Group, A. (Collaboration Author) ; Guénel, P. ; Hahnen, E. ; Haiman, C. A. ; Håkansson, N. ; Hall, P. ; Hamann, U.DKFZ* ; Harrington, P. A. ; Hart, S. N. ; Hooning, M. J. ; Hopper, J. L. ; Howell, A. ; Hunter, D. J. ; Investigators, A. (Collaboration Author) ; Investigators, k. (Collaboration Author) ; Jager, A. ; Jakubowska, A. ; John, E. M. ; Kaaks, R.DKFZ* ; 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. A. E. M. ; 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.DKFZ* ; Schmidt, M. K. ; Orr, N. ; Fletcher, O. ; Børresen-Dale, A.-L. ; Alnæs, G. I. G. ; Sahlberg, K. K. ; Ottestad, L. ; Kåresen, R. ; Schlichting, E. ; Holmen, M. M. ; Sauer, T. ; Haakensen, V. ; Engebråten, O. ; Naume, B. ; Fosså, A. ; Kiserud, C. E. ; Reinertsen, K. V. ; Helland, Å. ; Riis, M. ; Geisler, J. ; Bowtell, D. D. L. ; deFazio, A. ; Webb, P. M. ; Chenevix-Trench, G. ; Clarke, C. ; Marsh, D. ; Scott, R. ; Baxter, R. ; Yip, D. ; Carpenter, J. ; Davis, A. ; Pathmanathan, N. ; Simpson, P. ; Graham, D. ; Sachchithananthan, M. ; Amor, D. ; Andrews, L. ; Antill, Y. ; Balleine, R. ; Beesley, J. ; Bennett, I. ; Bogwitz, M. ; Botes, L. ; Brennan, M. ; Brown, M. ; Buckley, M. ; Burke, J. ; Butow, P. ; Caldon, L. ; Campbell, I. ; Chauhan, D. ; Chauhan, M. ; Chenevix-Trench, G. ; Christian, A. ; Cohen, P. ; Colley, A. ; Crook, A. ; Cui, J. ; Cummings, M. ; Dawson, S.-J. ; DeFazio, A. ; Delatycki, M. ; Dickson, R. ; Dixon, J. ; Edkins, T. ; Edwards, S. ; Farshid, G. ; Fellows, A. ; Fenton, G. ; Field, M. ; Flanagan, J. ; Fong, P. ; Forrest, L. ; Fox, S. ; French, J. ; Friedlander, M. ; Gaff, C. ; Gattas, M. ; George, P. ; Greening, S. ; Harris, M. ; Hart, S. ; Hayward, N. ; Hopper, J. ; Hoskins, C. ; Hunt, C. ; James, P. ; Jenkins, M. ; Kidd, A. ; Kirk, J. ; Koehler, J. ; Kollias, J. ; Lakhani, S. ; Lawrence, M. ; Lindeman, G. ; Lipton, L. ; Lobb, L. ; Mann, G. ; Marsh, D. ; McLachlan, S. A. ; Meiser, B. ; Milne, R. ; Nightingale, S. ; O'Connell, S. ; O'Sullivan, S. ; Ortega, D. G. ; Pachter, N. ; Patterson, B. ; Pearn, A. ; Phillips, K. ; Pieper, E. ; Rickard, E. ; Robinson, B. ; Saleh, M. ; Salisbury, E. ; Saunders, C. ; Saunus, J. ; Scott, R. ; Scott, C. ; Sexton, A. ; Shelling, A. ; Simpson, P. ; Southey, M. ; Spurdle, A. ; Taylor, J. ; Taylor, R. ; Thorne, H. ; Trainer, A. ; Tucker, K. ; Visvader, J. ; Walker, L. ; Williams, R. ; Winship, I. ; Young, M. A.
2021
Nature Publ. Group
Edinburgh
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Please use a persistent id in citations: doi:10.1038/s41416-020-01185-w
Abstract: 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.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.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).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.
Note: 2021 Feb;124(4):842-854
Contributing Institute(s):
- C071 Cancer Survivorship (C071)
- C020 Epidemiologie von Krebs (C020)
- C070 Klinische Epidemiologie und Alternf. (C070)
- Präventive Onkologie (C120)
- DKTK HD zentral (HD01)
- Molekulare Epidemiologie (C080)
- C055 Genomische Epidemiologie (C055)
- B072 Molekulargenetik des Mammakarzinoms (B072)
- B070 Funktionelle Genomanalyse (B070)
Research Program(s):
- 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)
Appears in the scientific report
2021
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