title: CYP3A7*1C allele is associated with reduced levels of 2-hydroxylation pathway oestrogen metabolites.
abstract: 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.
  
  
  
  We measured successfully 12 EMs in mid-follicular phase urine samples from 30 CYP3A7*1C carriers and 30 non-carriers using HPLC-MS/MS.
  
  
  
  In addition to having lower urinary E1levels, 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).
  
  
  
  The CYP3A7*1C allele is associated with a lower urinary E1levels, 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.
authors.affiliation: Faculty of Medicine, Department of Surgery and Cancer, Imperial College, London SW7 2AZ, UK.
authors.forename: Deepti
authors.initials: D
authors.lastname: Sood
authors.affiliation: Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW7 3RP, UK.
authors.forename: Nichola
authors.initials: N
authors.lastname: Johnson
authors.affiliation: Faculty of Medicine, Department of Surgery and Cancer, Imperial College, London SW7 2AZ, UK.
authors.forename: Pooja
authors.initials: P
authors.lastname: Jain
authors.affiliation: Faculty of Medicine, Department of Surgery and Cancer, Imperial College, London SW7 2AZ, UK.
authors.forename: Alexandros P
authors.initials: AP
authors.lastname: Siskos
authors.affiliation: Department of Life Sciences, Imperial College, London SW7 2AZ, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Bennett
authors.affiliation: Department of Non-Communicable Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Gilham
authors.affiliation: Department of Non-Communicable Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Marta Cecilia
authors.initials: MC
authors.lastname: Busana
authors.affiliation: Department of Non-Communicable Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.affiliation: Department of Non-Communicable Disease Epidemiology, The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Isabel
authors.initials: I
authors.lastname: Dos-Santos-Silva
authors.affiliation: Faculty of Medicine, Department of Surgery and Cancer, Imperial College, London SW7 2AZ, UK.
authors.forename: Hector C
authors.initials: HC
authors.lastname: Keun
authors.affiliation: Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW7 3RP, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000652:urine; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000652:urine; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D006900:Hydroxylation; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D017697:Premenopause / Q000235:genetics / Q000652:urine; D012307:Risk Factors; D055815:Young Adult
chemical_list: D004967:Estrogens; D004970:Estrone; C103123:CYP3A7 protein, human; D051544:Cytochrome P-450 CYP3A