Frequency of hemochromatosis gene (HFE) mutations in Russian healthy women and patients with estrogen-dependent cancers |
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Authors: | Kondrashova Tatiana V Neriishi Kazuo Ban Sadayuki Ivanova Tatiana I Krikunova Lyudmila I Shentereva Nataliya I Smirnova Iya A Zharikova Irina A Konova Marina V Taira Senjun Tsyb Anatoly F |
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Affiliation: | Medical Radiological Research Center, Russian Academy of Medical Sciences, Ul. Koroleva 4, Obninsk 249036, Russia. kondrashova@mrrc.obninsk.ru |
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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. |
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