title: Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers.
abstract: Possible association between the C282Y and H63D mutations in the HFE gene and estrogen-dependent cancer risk was assessed. Genotyping was performed using PCR amplification followed by digestion of products with specific restrictases. In a population of 260 healthy women (permanent residents of the southwest European Russia), mutant allele frequencies at the C282Y and H63D sites were evaluated as 3.3 and 16.3%, respectively. In patients with breast, ovarian, and endometrial cancer, C282Y frequencies were also low (1.0, 1.3, and 3.8%, respectively), and no cancer risk associated with the C282Y mutation was found. Odds ratios for breast cancer risk associated with the H63D mutation increased significantly with age: 0.5 in women below 48 years old, 1.0 in a range of 48-57 years, and 4.4 in older women (P(trend)=0.002). The latter value was statistically significant (95% CI, 1.4-14.1), indicating that women bearing the H63D mutation may be at an increased breast cancer risk at an age above 57 years. Preliminary results obtained in patients with two other estrogen-dependent malignancies revealed the same tendency to OR increase with age in ovarian cancer patients (P(trend)=0.008), but no age-related OR differences in endometrial cancer patients.
authors.affiliation: Medical Radiological Research Center, Russian Academy of Medical Sciences, Ul. Koroleva 4, Obninsk 249036, Russia. kondrashova@mrrc.obninsk.ru
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Kondrashova
authors.forename: Kazuo
authors.initials: K
authors.lastname: Neriishi
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Ban
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Ivanova
authors.forename: Lyudmila I
authors.initials: LI
authors.lastname: Krikunova
authors.forename: Nataliya I
authors.initials: NI
authors.lastname: Shentereva
authors.forename: Iya A
authors.initials: IA
authors.lastname: Smirnova
authors.forename: Irina A
authors.initials: IA
authors.lastname: Zharikova
authors.forename: Marina V
authors.initials: MV
authors.lastname: Konova
authors.forename: Senjun
authors.initials: S
authors.lastname: Taira
authors.forename: Anatoly F
authors.initials: AF
authors.lastname: Tsyb
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006262:Health; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D012426:Russia
chemical_list: D004967:Estrogens; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins