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

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NBCS Collaborators , AOCS Grp , ABCTB Investigators , kConFab Investigators , Johnson , N , Maguire , S , Morra , A , Blomqvist , C & Nevanlinna , H 2021 , ' 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 , pp. 842-854 . https://doi.org/10.1038/s41416-020-01185-w

Title: CYP3A7*1C allele : linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
Author: NBCS Collaborators; AOCS Grp; ABCTB Investigators; kConFab Investigators; Johnson, Nichola; Maguire, Sarah; Morra, Anna; Blomqvist, Carl; Nevanlinna, Heli
Contributor: University of Helsinki, HUS Comprehensive Cancer Center
University of Helsinki, HUS Gynecology and Obstetrics
Date: 2021-02-16
Language: eng
Number of pages: 13
Belongs to series: British Journal of Cancer
ISSN: 0007-0920
URI: http://hdl.handle.net/10138/328135
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.
Subject: GENOME-WIDE ASSOCIATION
IMPUTATION
CYP3A5
3122 Cancers
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