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

Johnson, N; Maguire, S; Morra, A; Kapoor, PM; Tomczyk, K; Jones, ME; Schoemaker, MJ; Gilham, C; Bolla, MK; Wang, Q; Dennis, J; Ahearn, TU; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Arndt, V; Aronson, KJ; Augustinsson, A; Baynes, C; Freeman, LEB; Beckmann, MW; Benitez, J; Bermisheva, M; Blomqvist, C; Boeckx, B; Bogdanova, NV; Bojesen, SE; Brauch, H; Brenner, H; Burwinkel, B; Campa, D; Canzian, F; Castelao, JE; Chanock, SJ; Chenevix-Trench, G; Clarke, CL; Conroy, DM; Couch, FJ; Cox, A; Cross, SS; Czene, K; Dörk, T; Eliassen, AH; Engel, C; Evans, DG; Fasching, PA; Figueroa, J; Floris, G; Flyger, H; Gago-Dominguez, M; Gapstur, SM; García-Closas, M; Gaudet, MM; Giles, GG; Goldberg, MS; González-Neira, A; Guénel, P; Hahnen, E; Haiman, CA; Håkansson, N; Hall, P; Hamann, U; Harrington, PA; Hart, SN; Hooning, MJ; Hopper, JL; Howell, A; Hunter, DJ; Jager, A; Jakubowska, A; John, EM; Kaaks, R; Keeman, R; Khusnutdinova, E; Kitahara, CM; Kosma, V-M; Koutros, S; Kraft, P; Kristensen, VN; Kurian, AW; Lambrechts, D; Le Marchand, L; Linet, M; Lubiński, J; Mannermaa, A; Manoukian, S; Margolin, S; Martens, JWM; Mavroudis, D; Mayes, R; Meindl, A; Milne, RL; Neuhausen, SL; Nevanlinna, H; Newman, WG; Nielsen, SF; Nordestgaard, BG; Obi, N; Olshan, AF; Olson, JE; Olsson, H; Orban, E; Park-Simon, T-W; Peterlongo, P; Plaseska-Karanfilska, D; Pylkäs, K; Rennert, G; Rennert, HS; Ruddy, KJ; Saloustros, E; Sandler, DP; Sawyer, EJ; Schmutzler, RK; Scott, C; Shu, X-O; Simard, J; Smichkoska, S; Sohn, C; Southey, MC; Spinelli, JJ; Stone, J; Tamimi, RM; Taylor, JA; Tollenaar, RAEM; Tomlinson, I; Troester, MA; Truong, T; Vachon, CM; van Veen, EM; Wang, SS; Weinberg, CR; Wendt, C; Wildiers, H; Winqvist, R; Wolk, A; Zheng, W; Ziogas, A; Dunning, AM; Pharoah, PDP; Easton, DF; Howie, AF; Peto, J; dos-Santos-Silva, I; Swerdlow, AJ; Chang-Claude, J; Schmidt, MK; Orr, N; Fletcher, O

Women's Health Collection

Journal article

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

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 x 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 x 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.Peer reviewe

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

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., … Fletcher, O. (2021). CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers. British Journal of Cancer, 124(4), 842–854.

MLA Style

Johnson, N, et al. “CYP3A7*1C Allele: Linking Premenopausal Oestrone and Progesterone Levels with Risk of Hormone Receptor-Positive Breast Cancers.” British Journal of Cancer, vol. 124, no. 4, 2021, pp. 842–54.

Chicago Style

Johnson, N, S Maguire, A Morra, et al. 2021. “CYP3A7*1C Allele: Linking Premenopausal Oestrone and Progesterone Levels with Risk of Hormone Receptor-Positive Breast Cancers.” British Journal of Cancer 124 (4): 842–54.
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