title: Polymorphisms in the human aromatase cytochrome P450 gene (CYP19) and breast cancer risk.
abstract: The aromatase enzyme catalyses the conversion of androgens to oestrogens in the oestrogen biosynthesis pathway. Because increased exposure to oestrogens is considered to be a risk factor for breast cancer, the human aromatase gene (CYP19) is a plausible candidate for low penetrance breast cancer susceptibility. Preliminary reports have suggested that specific alleles of a TTTA repeat may be associated with differences in breast cancer risk. We have identified two new polymorphisms in the CYP19 gene: a TCT insertion/deletion in intron 4 and a G-->T substitution in intron 6, which have rare allele frequencies of 0.35 and 0.45, respectively, in the British population. Comparison was made between the frequencies of these alleles and those of the TTTA repeat in up to 599 breast cancer cases and 433 normal controls from the East Anglian, British population. We found strong linkage disequilibrium between the alleles of these three loci, but no significant association of any alleles with breast cancer risk. The maximum odds ratios observed were: 1.03 (95% CI 0.68-1.55) for the intron 4 TCT insertion/deletion polymorphism [del/del versus ins/ins]; 1.56 (95% CI 0.63-3.83) for the intron 4 [TTTA](10) allele; 1.29 (95% CI 0. 75-2.21) for the intron 6 G-->T polymorphism [TT versus GG]. We conclude that the CYP19 gene has no major role in common breast cancer incidence in the British population.
authors.affiliation: CRC Department of Oncology, CRC Genetic Epidemiology Group and EPIC, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, UK. katie.healey@srl.cam.ac.uk
authors.forename: C S
authors.initials: CS
authors.lastname: Healey
authors.forename: A M
authors.initials: AM
authors.lastname: Dunning
authors.forename: F
authors.initials: F
authors.lastname: Durocher
authors.forename: D
authors.initials: D
authors.lastname: Teare
authors.forename: P D
authors.initials: PD
authors.lastname: Pharoah
authors.forename: R N
authors.initials: RN
authors.lastname: Luben
authors.forename: D F
authors.initials: DF
authors.lastname: Easton
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001141:Aromatase / Q000235:genetics* / Q000502:physiology; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D008875:Middle Aged; D016017:Odds Ratio; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D012739:Gonadal Steroid Hormones; D001141:Aromatase