Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers.
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.
Kondrashova
Tatiana V
TV
Medical Radiological Research Center, Russian Academy of Medical Sciences, Ul. Koroleva 4, Obninsk 249036, Russia. kondrashova@mrrc.obninsk.ru
Neriishi
Kazuo
K
Ban
Sadayuki
S
Ivanova
Tatiana I
TI
Krikunova
Lyudmila I
LI
Shentereva
Nataliya I
NI
Smirnova
Iya A
IA
Zharikova
Irina A
IA
Konova
Marina V
MV
Taira
Senjun
S
Tsyb
Anatoly F
AF
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
D004967:Estrogens; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins