CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites

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Title: CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites
Authors: Sood, D
Johnson, N
Jain, P
Siskos, AP
Bennett, M
Gilham, C
Busana, MC
Peto, J
Dos-Santos-Silva, I
Keun, HC
Fletcher, O
Item Type: Journal Article
Abstract: background: Endogenous sex hormones are well-established risk factors for breast cancer; the contribution of specific oestrogen metabolites (EMs) and/or ratios of specific EMs is less clear. We have previously identified a CYP3A7*1C allele that is associated with lower urinary oestrone (E1) levels in premenopausal women. The purpose of this analysis was to determine whether this allele was associated with specific pathway EMs. methods: We measured successfully 12 EMs in mid-follicular phase urine samples from 30 CYP3A7*1C carriers and 30 non-carriers using HPLC-MS/MS. results: In addition to having lower urinary E1 levels, CYP3A7*1C carriers had significantly lower levels of four of the 2-hydroxylation pathway EMs that we measured (2-hydroxyestrone, P=1.1 × 10−12; 2-hydroxyestradiol, P=2.7 × 10−7; 2-methoxyestrone, P=1.9 × 10−12; and 2-methoxyestradiol, P=0.0009). By contrast, 16α-hydroxylation pathway EMs were slightly higher in carriers and significantly so for 17-epiestriol (P=0.002). conclusions: The CYP3A7*1C allele is associated with a lower urinary E1 levels, a more pronounced reduction in 2-hydroxylation pathway EMs and a lower ratio of 2-hydroxylation:16α-hydroxylation EMs in premenopausal women. To further characterise the association between parent oestrogens, EMs and subsequent risk of breast cancer, characterisation of additional genetic variants that influence oestrogen metabolism and large prospective studies of a broad spectrum of EMs will be required.
Issue Date: 10-Jan-2017
Date of Acceptance: 1-Dec-2016
ISSN: 1532-1827
Publisher: Cancer Research UK
Start Page: 382
End Page: 388
Journal / Book Title: British Journal of Cancer
Volume: 116
Issue: 3
Copyright Statement: © 2017 The Author(s). This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit
Keywords: Science & Technology
Life Sciences & Biomedicine
CYP3A7*1C allele
oestrogen metabolites
breast cancer
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine
Faculty of Natural Sciences

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