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. / Johnson, Nichola; Maguire, Sarah; Morra, Anna; Kapoor, Pooja Middha; Tomczyk, Katarzyna; Jones, Michael E.; Schoemaker, Minouk J.; Gilham, Clare; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Ahearn, Thomas U.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; Aronson, Kristan J.; Augustinsson, Annelie; Baynes, Caroline; Freeman, Laura E.Beane; Beckmann, Matthias W.; Benitez, Javier; Bermisheva, Marina; Blomqvist, Carl; Boeckx, Bram; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Campa, Daniele; Canzian, Federico; Castelao, Jose E.; Chanock, Stephen J.; Chenevix-Trench, Georgia; Clarke, Christine L.; Børresen-Dale, Anne Lise; Alnæs, Grethe I.Grenaker; Sahlberg, Kristine K.; Ottestad, Lars; Kåresen, Rolf; Schlichting, Ellen; Holmen, Marit Muri; Sauer, Toril; Haakensen, Vilde; Riis, Margit; Flyger, Henrik; Nielsen, Sune F.; Nordestgaard, Børge G.; Scott, Christopher; NBCS Collaborators; AOCS Group; ABCTB Investigators; kConFab Investigators.
I: British Journal of Cancer, Bind 124, Nr. 4, 2021, s. 842-854.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 - Børresen-Dale, Anne Lise
AU - Alnæs, Grethe I.Grenaker
AU - Sahlberg, Kristine K.
AU - Ottestad, Lars
AU - Kåresen, Rolf
AU - Schlichting, Ellen
AU - Holmen, Marit Muri
AU - Sauer, Toril
AU - Haakensen, Vilde
AU - Riis, Margit
AU - Flyger, Henrik
AU - Nielsen, Sune F.
AU - Nordestgaard, Børge G.
AU - Scott, Christopher
AU - NBCS Collaborators
AU - AOCS Group
AU - ABCTB Investigators
AU - kConFab Investigators
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
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.
U2 - 10.1038/s41416-020-01185-w
DO - 10.1038/s41416-020-01185-w
M3 - Journal article
C2 - 33495599
AN - SCOPUS:85099996359
VL - 124
SP - 842
EP - 854
JO - The British journal of cancer. Supplement
JF - The British journal of cancer. Supplement
SN - 0007-0920
IS - 4
ER -
ID: 276333066