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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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@article{07b1f7d4aa704b3c84c69d3cf2efe7d9,
title = "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 × 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.",
author = "Nichola Johnson and Sarah Maguire and Anna Morra and Kapoor, {Pooja Middha} and Katarzyna Tomczyk and Jones, {Michael E} and Schoemaker, {Minouk J} and Clare Gilham and Bolla, {Manjeet K} and Qin Wang and Joe Dennis and Ahearn, {Thomas U} and Andrulis, {Irene L} and Hoda Anton-Culver and Antonenkova, {Natalia N} and Volker Arndt and Aronson, {Kristan J} and Annelie Augustinsson and Caroline Baynes and Freeman, {Laura E Beane} and Beckmann, {Matthias W} and Javier Benitez and Marina Bermisheva and Carl Blomqvist and Bram Boeckx and Bogdanova, {Natalia V} and Bojesen, {Stig E} and Hiltrud Brauch and Hermann Brenner and Barbara Burwinkel and Daniele Campa and Federico Canzian and Castelao, {Jose E} and Chanock, {Stephen J} and Georgia Chenevix-Trench and Clarke, {Christine L} and Conroy, {Don M} and Couch, {Fergus J} and Angela Cox and Cross, {Simon S} and Kamila Czene and Thilo D{\"o}rk and Eliassen, {A Heather} and Christoph Engel and Evans, {D Gareth} and Fasching, {Peter A} and Jonine Figueroa and Henrik Flyger and Nielsen, {Sune F} and Nordestgaard, {B{\o}rge G} and {NBCS Collaborators}",
note = "Publisher Copyright: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
day = "16",
doi = "10.1038/s41416-020-01185-w",
language = "English",
volume = "124",
pages = "842--854",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - CYP3A7*1C allele

T2 - linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

AU - Johnson, Nichola

AU - Maguire, Sarah

AU - Morra, Anna

AU - Kapoor, Pooja Middha

AU - Tomczyk, Katarzyna

AU - Jones, Michael E

AU - Schoemaker, Minouk J

AU - Gilham, Clare

AU - Bolla, Manjeet K

AU - Wang, Qin

AU - Dennis, Joe

AU - Ahearn, Thomas U

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N

AU - Arndt, Volker

AU - Aronson, Kristan J

AU - Augustinsson, Annelie

AU - Baynes, Caroline

AU - Freeman, Laura E Beane

AU - Beckmann, Matthias W

AU - Benitez, Javier

AU - Bermisheva, Marina

AU - Blomqvist, Carl

AU - Boeckx, Bram

AU - Bogdanova, Natalia V

AU - Bojesen, Stig E

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Burwinkel, Barbara

AU - Campa, Daniele

AU - Canzian, Federico

AU - Castelao, Jose E

AU - Chanock, Stephen J

AU - Chenevix-Trench, Georgia

AU - Clarke, Christine L

AU - Conroy, Don M

AU - Couch, Fergus J

AU - Cox, Angela

AU - Cross, Simon S

AU - Czene, Kamila

AU - Dörk, Thilo

AU - Eliassen, A Heather

AU - Engel, Christoph

AU - Evans, D Gareth

AU - Fasching, Peter A

AU - Figueroa, Jonine

AU - Flyger, Henrik

AU - Nielsen, Sune F

AU - Nordestgaard, Børge G

AU - NBCS Collaborators

N1 - Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/16

Y1 - 2021/2/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85099996359&partnerID=8YFLogxK

U2 - 10.1038/s41416-020-01185-w

DO - 10.1038/s41416-020-01185-w

M3 - Journal article

C2 - 33495599

VL - 124

SP - 842

EP - 854

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

ER -

ID: 61899580