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, 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
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
Document Type
Journal Article
Date
2021-02-16
Date Accepted
2020-11-05
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). 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.
Citation
Br J Cancer, 2021
Source Title
Publisher
SPRINGERNATURE
ISSN
eISSN
1532-1827
Research Team
Functional Genetic Epidemiology
Aetiological Epidemiology
Functional Genetic Epidemiology
Aetiological Epidemiology
Aetiological Epidemiology
Functional Genetic Epidemiology
Aetiological Epidemiology