title: Effect of CYP19 rs6493497 and rs7176005 haplotype status on in vivo aromatase transcription, plasma and tissue estrogen levels in postmenopausal women.
abstract: High plasma levels of estradiol (E(2)) are correlated to increased breast cancer risk in postmenopausal women. Recently, a study reported two single nucleotide polymorphisms (SNPs) (rs6493497; C→T and rs7176005; G→A) in the aromatase (CYP19) promoter 1.1 to be associated with elevated plasma E(2) levels, most likely due to enhanced transcription. In silico predictions suggested increased transcription factor binding for the rs7176005_A allele. We genotyped 46 breast cancer patients for rs6493497 and rs7176005 status and assessed the potential association between CYP19 SNP status and (i) CYP19 mRNA levels in tumour and normal breast tissue, and (ii) estrogen levels in plasma, tumour and normal breast tissue. In addition, we measured CYP19 SNP status and correlated it to plasma estrogen levels in a confirmatory dataset of 108 healthy postmenopausal women. We found no correlation between either of the two SNPs and CYP19 mRNA level. In the breast cancer patients, the rs6493497_T/rs7176005_A variant haplotype was associated with low plasma estrone (E(1)) (p=0.038) and low E(2) (p=0.050) levels; however, no correlation was recorded between SNP status and plasma estrogen levels in the cohort of 108 healthy postmenopausal women. Our findings indicate rs6493497 and rs7176005 status not to enhance CYP19 transcription or increase estrogen levels in postmenopausal women.
authors.affiliation: Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway.
authors.forename: Anne Hege
authors.initials: AH
authors.lastname: Straume
authors.forename: Stian
authors.initials: S
authors.lastname: Knappskog
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004967:Estrogens / Q000097:blood* / Q000378:metabolism; D004970:Estrone / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D004967:Estrogens; D004970:Estrone; D001141:Aromatase