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, or 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 (ptrend=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 (ptrend=0.008), but no age-related OR differences in endometrial cancer patients

Thyroid autoantibodies and thyroid function in subjects exposed to Chernobyl fallout during childhood: evidence for a transient radiation-induced elevation of serum thyroid antibodies without an increase in thyroid autoimmune disease

Context: An increase in the prevalence of thyroid autoantibodies (ATAs) was reported 6–8 yr after the Chernobyl accident in radiation-exposed children and adolescents. Objective: Our objective was to reassess the effects of childhood radiation exposure on ATAs and thyroid function 13–15 yr after the accident. Design and Setting: We measured the antithyroglobulin (TgAbs) and antithyroperoxidase (TPOAbs) antibodies and TSH in 1433 sera collected between 1999 and 2001 from 13- to 17-yr-old adolescents born between January 1982 and October 1986 in paired contaminated and noncontaminated villages of Belarus, Ukraine, and Russia.Atotal of 1441 sera was collected from age- and sex-matched controls living in Denmark and Sardinia (Italy). Free T4 and free T3 were measured when TSH was abnormal. Results: TPOAb prevalence was higher in contaminated than in noncontaminated Belarusian children (6.4 vs. 2.4%; P r0.02) but lower than previously reported (11%) in a different contaminated Belarus village.Nodifference inTPOAbprevalencewasfound in UkrainianandRussian villages.TgAbsshowed no difference between contaminated and noncontaminated Belarus and Ukraine, whereas in Russia they showed a relative increase in the exposed subjects with respect to the unexposed, who showed an unexpectedly lower prevalence of TgAbs. Besides radiation exposure, female gender was the only variable significantly correlated with ATAs in all groups. ATA prevalence in nonexposed villages of Belarus, Ukraine,andRussian Federation did not differ from that found in SardiniaandDenmark. With few exceptions, thyroid function was normal in all study groups. Conclusions: TPOAb prevalence in adolescents exposed to radioactive fallout was still increased in Belarus 13–15 yr after the Chernobyl accident. This increase was less evident than previously reported and was not accompanied by thyroid dysfunction. Our data suggest that radioactive fallout elicited a transient autoimmune reaction, without triggering full-blown thyroid autoimmune disease. Longer observation periods are needed to exclude later effects