title: [Analysis of polymorphisms in genes of insulin receptor substrate-1 and enzymes involved in estrogen biosynthesis and metabolism among breast cancer patients with BRCA1 mutations].
abstract: Polymorphisms in genes involved in steroidogenesis as well as sensitivity to insulin as potential cancer risk factors have received constantly-growing attention over this decade. The peculiarities of endocrine and metabolic features of cancer identified earlier in BRCA1 mutation carriers prompted an investigation of the frequency of polymorphisms in the genes of IRS-1 and enzymes of estrogen biosynthesis and metabolism, such as aromatase (CYP19), estrogen 4-hydroxylase and catechol-O-methyl transferase (COMT) in 12 BRCA1 mutation carriers and in 22 non-carriers. The results were compared with the earlier data from the patients with the same diagnosis (n = 110 and n = 295, respectively) but untested for BRCA1 mutation. BRCA1 mutation carriers tended to show increasing fractions of heterozygotes for AG (COMT Vall58Met p = 0.24) and active allele A6 featuring 11 TTTA repeats in the 4-th introne [corrected] of CYP19 gene (p 0.09). [corrected] The frequency of co-occurring CC (CYP1B1) Arg48Gly), AG (COMT Vall58Met ) and A6 (CYP19) in BRCA1 mutation carriers (5 out of 12, 41.6% ) was significantly higher than that in non-carriers (2 out of 22, 9.1% ) (p = 0.03). Immunohistochemical assay showed aromatase expression levels to be the highest among cases of BRCA1 mutation and A6 (CYP19) while CYP1B1 expression was the highest in those of combination of BRCA1 mutation and low-activity AA genotype (COMT Vall58Mer). Our results warrant further large-scale cooperative studies of the problem.
authors.forename: L M
authors.initials: LM
authors.lastname: Bershteĭn
authors.forename: Iu M
authors.initials: IuM
authors.lastname: Ulybina
authors.forename: K M
authors.initials: KM
authors.lastname: Pozharisskiĭ
authors.forename: E N
authors.initials: EN
authors.lastname: Imianitov
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004967:Estrogens / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: D004967:Estrogens; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase