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

http://urn.fi/urn:nbn:fi-fe202103308792
Teksti
Johnson, N. (Nichola) ; Maguire, S. (Sarah) ; Morra, A. (Anna) ; Kapoor, P. M. (Pooja Middha) ; Tomczyk, K. (Katarzyna) ; Jones, M. E. (Michael E.) ; Schoemaker, M. J. (Minouk J.) ; Gilham, C. (Clare) ; Bolla, M. K. (Manjeet K.) ; Wang, Q. (Qin) ; Dennis, J. (Joe) ; Ahearn, T. U. (Thomas U.) ; Andrulis, I. L. (Irene L.) ; Anton-Culver, H. (Hoda) ; Antonenkova, N. N. (Natalia N.) ; Arndt, V. (Volker) ; Aronson, K. J. (Kristan J.) ; Augustinsson, A. (Annelie) ; Baynes, C. (Caroline) ; Freeman, L. E. (Laura E. Beane) ; Beckmann, M. W. (Matthias W.) ; Benitez, J. (Javier) ; Bermisheva, M. (Marina) ; Blomqvist, C. (Carl) ; Boeckx, B. (Bram) ; Bogdanova, N. V. (Natalia V.) ; Bojesen, S. E. (Stig E.) ; Brauch, H. (Hiltrud) ; Brenner, H. (Hermann) ; Burwinkel, B. (Barbara) ; Campa, D. (Daniele) ; Canzian, F. (Federico) ; Castelao, J. E. (Jose E.) ; Chanock, S. J. (Stephen J.) ; Chenevix-Trench, G. (Georgia) ; Clarke, C. L. (Christine L.) ; Conroy, D. M. (Don M.) ; Couch, F. J. (Fergus J.) ; Cox, A. (Angela) ; Cross, S. S. (Simon S.) ; Czene, K. (Kamila) ; Doerk, T. (Thilo) ; Eliassen, A. H. (A. Heather) ; Engel, C. (Christoph) ; Evans, D. G. (D. Gareth) ; Fasching, P. A. (Peter A.) ; Figueroa, J. (Jonine) ; Floris, G. (Giuseppe) ; Flyger, H. (Henrik) ; Gago-Dominguez, M. (Manuela) ; Gapstur, S. M. (Susan M.) ; Garcia-Closas, M. (Montserrat) ; Gaudet, M. M. (Mia M.) ; Giles, G. G. (Graham G.) ; Goldberg, M. S. (Mark S.) ; Gonzalez-Neira, A. (Anna) ; Guenel, P. (Pascal) ; Hahnen, E. (Eric) ; Haiman, C. A. (Christopher A.) ; Hakansson, N. (Niclas) ; Hall, P. (Per) ; Hamann, U. (Ute) ; Harrington, P. A. (Patricia A.) ; Hart, S. N. (Steven N.) ; Hooning, M. J. (Maartje J.) ; Hopper, J. L. (John L.) ; Howell, A. (Anthony) ; Hunter, D. J. (David J.) ; Jager, A. (Agnes) ; Jakubowska, A. (Anna) ; John, E. M. (Esther M.) ; Kaaks, R. (Rudolf) ; Keeman, R. (Renske) ; Khusnutdinova, E. (Elza) ; Kitahara, C. M. (Cari M.) ; Kosma, V.-M. (Veli-Matti) ; Koutros, S. (Stella) ; Kraft, P. (Peter) ; Kristensen, V. N. (Vessela N.) ; Kurian, A. W. (Allison W.) ; Lambrechts, D. (Diether) ; Le Marchand, L. (Loic) ; Linet, M. (Martha) ; Lubinski, J. (Jan) ; Mannermaa, A. (Arto) ; Manoukian, S. (Siranoush) ; Margolin, S. (Sara) ; Martens, J. W. (John W. M.) ; Mavroudis, D. (Dimitrios) ; Mayes, R. (Rebecca) ; Meindl, A. (Alfons) ; Milne, R. L. (Roger L.) ; Neuhausen, S. L. (Susan L.) ; Nevanlinna, H. (Heli) ; Newman, W. G. (William G.) ; Nielsen, S. F. (Sune F.) ; Nordestgaard, B. G. (Borge G.) ; Obi, N. (Nadia) ; Olshan, A. F. (Andrew F.) ; Olson, J. E. (Janet E.) ; Olsson, H. (Hakan) ; Orban, E. (Ester) ; Park-Simon, T.-W. (Tjoung-Won) ; Peterlongo, P. (Paolo) ; Plaseska-Karanfilska, D. (Dijana) ; Pylkäs, K. (Katri) ; Rennert, G. (Gad) ; Rennert, H. S. (Hedy S.) ; Ruddy, K. J. (Kathryn J.) ; Saloustros, E. (Emmanouil) ; Sandler, D. P. (Dale P.) ; Sawyer, E. J. (Elinor J.) ; Schmutzler, R. K. (Rita K.) ; Scott, C. (Christopher) ; Shu, X.-O. (Xiao-Ou) ; Simard, J. (Jacques) ; Smichkoska, S. (Snezhana) ; Sohn, C. (Christof) ; Southey, M. C. (Melissa C.) ; Spinelli, J. J. (John J.) ; Stone, J. (Jennifer) ; Tamimi, R. M. (Rulla M.) ; Taylor, J. A. (Jack A.) ; Tollenaar, R. A. (Rob A. E. M.) ; Tomlinson, I. (Ian) ; Troester, M. A. (Melissa A.) ; Truong, T. (Therese) ; Vachon, C. M. (Celine M.) ; van Veen, E. M. (Elke M.) ; Wang, S. S. (Sophia S.) ; Weinberg, C. R. (Clarice R.) ; Wendt, C. (Camilla) ; Wildiers, H. (Hans) ; Winqvist, R. (Robert) ; Wolk, A. (Alicja) ; Zheng, W. (Wei) ; Ziogas, A. (Argyrios) ; Dunning, A. M. (Alison M.) ; Pharoah, P. D. (Paul D. P.) ; Easton, D. F. (Douglas F.) ; Howie, A. F. (A. Forbes) ; Peto, J. (Julian) ; dos-Santos-Silva, I. (Isabel) ; Swerdlow, A. J. (Anthony J.) ; Chang-Claude, J. (Jenny) ; Schmidt, M. K. (Marjanka K.) ; Orr, N. (Nick) ; Fletcher, O. (Olivia)
Springer Nature

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 × 10⁻¹⁸).

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.

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