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dc.contributor.authorSood, D
dc.contributor.authorJohnson, N
dc.contributor.authorJain, P
dc.contributor.authorSiskos, AP
dc.contributor.authorBennett, M
dc.contributor.authorGilham, C
dc.contributor.authorBusana, MC
dc.contributor.authorPeto, J
dc.contributor.authorDos-Santos-Silva, I
dc.contributor.authorKeun, HC
dc.contributor.authorFletcher, O
dc.date.accessioned2016-12-12T13:34:48Z
dc.date.issued2017-01-10
dc.identifier.citationBritish journal of cancer, 2017, 116 (3), pp. 382 - 388
dc.identifier.issn0007-0920
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/321
dc.identifier.eissn1532-1827
dc.identifier.doi10.1038/bjc.2016.432
dc.description.abstractBackground 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 (E 1 ) 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 E 1 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 E 1 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.
dc.formatPrint-Electronic
dc.format.extent382 - 388
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectEstrone
dc.subjectEstrogens
dc.subjectRisk Factors
dc.subjectDown-Regulation
dc.subjectHydroxylation
dc.subjectPremenopause
dc.subjectAlleles
dc.subjectAdolescent
dc.subjectAdult
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectCytochrome P-450 CYP3A
dc.subjectMetabolic Networks and Pathways
dc.subjectYoung Adult
dc.subjectGenetic Carrier Screening
dc.titleCYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites.
dc.typeJournal Article
dcterms.dateAccepted2016-12-01
rioxxterms.versionofrecord10.1038/bjc.2016.432
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-01-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBritish journal of cancer
pubs.issue3
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.publication-statusPublished
pubs.volume116
pubs.embargo.termsNo embargo
icr.researchteamFunctional Genetic Epidemiologyen_US
dc.contributor.icrauthorFletcher, Oliviaen


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