The study investigated an association between the germline polymorphism at TP53 codon 72 and the development of papillary thyroid cancer (PTC) following exposure to radiation from the Chernobyl accident. TP53 genotype was examined in 48 pediatric/adolescent (age at diagnosis <18 years) and 68 adult post-Chernobyl patient with PTC, 53 adult patients with sporadic PTC and 313 healthy individuals from Russian-Ukrainian population. In addition, we evaluated loss of heterozygosity for TP53 and the allele expression ratio. The genotype of the patients was correlated with clinicopathological data. Arg TP53 homozygotes were found to be significantly underrepresented among adults with post-Chernobyl PTC, but not in children and adolescents when compared with sporadic PTC cases and the general population. In the tumors, cell transformation did not lead to allelic loss or biased TP53 allele expression in heterozygous individuals. None of TP53 genotypes specifically associated with tumor stage and morphology, however there were particular correlations with lymph node status in certain age groups of radiation-associated cases not seen in sporadic PTCs. The findings suggest TP53 allele combinations other than Arg/Arg may contribute to the risk of development of PTC in individuals exposed to radiation during their late childhood, adolescence or in young adulthood.
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.
KóÀová M., E. Békeová, M. Levkut: The Effects of Chlorine Intake on Some Morphometric Parameters of the Thyroid Gland in Lambs. Acta Vet. Brno 1999, 68: 191-195.The aim of the study was to determine whether drinking water containing two concentrations of chlorine (0.3 mg . l -1 or 1.8 mg . l -1 ) affects morphometric indicators of follicular epithelial cells and the diameter of thyroid gland follicles in young lambs.The height of follicular epithelial cells, the diameter of thyroid gland follicles, the frequency of epithelial cell height categories, and the frequency of follicular diameter categories were studied in two groups of lambs after two treatments: one for four weeks and the other for three months. The first group had access to drinking water with 0.3 mg . l -1 chlorine (short-term intake and low Cl concentration) for four weeks. The second group had access to drinking water containing 1.8 mg . l -1 chlorine (long-term intake and high concentration) for three months.A significant increase (P < 0.01) in follicular epithelial cell height and a significant frequency distribution shift to the higher cellular height categories was observed after intake of chlorinated water (0.3 mg . l -1 ), (P < 0.01 for cell height categories 3.1-4 and 4.1-5 µm) for four weeks. There was also a significant shift (P < 0.01 for cell height categories 4.1-5 and 5.1-6 µm) in lambs receiving 1.8 mg . l -1 chlorine in their drinking water for three months as compared to controls.The diameter of thyroid gland follicles significantly decreased (P < 0.01), and the percent of small thyroid follicles significantly increased (for diameter categories 20.1-40 and 40.1-60 µm P < 0.01 and P < 0.05, respectively) in lambs receiving 1.8 mg . l -1 chlorine in drinking water for three months as compared to controls.Our morphometric findings suggest that chlorine interferes with the thyroid metabolism in lambs, however, with no macroscopically detectable changes of the thyroid.
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