CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.
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Date
2021-02-16Author
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
NBCS Collaborators,
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
AOCS Group,
Guénel, P
Hahnen, E
Haiman, CA
Håkansson, N
Hall, P
Hamann, U
Harrington, PA
Hart, SN
Hooning, MJ
Hopper, JL
Howell, A
Hunter, DJ
ABCTB Investigators,
kConFab Investigators,
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
Type
Journal Article
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). 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.
Collections
Research team
Functional Genetic Epidemiology
Aetiological Epidemiology
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2020-11-05
License start date
2021-01-26
Citation
Br J Cancer, 2021
Publisher
SPRINGERNATURE