Was compared frequency of lymphocytes mutant at loci of T-cell receptor (TCR) from samples of peripheral blood taken from 186 healthy donors and 46 untreated thyroid cancer patients, including the persons exposed to ionizing radiation as a result of inhabitation in radioactive polluted region of Russian Federation. Was shown that the cell mutation rate within thyroid cancer group was significantly higher than the same parameter for the healthy person with similar age distribution (p < 0.01). It could be a result of such factors as genotoxic influence, different sensitivity or possible genome instability (including radiation-induced). It was found that 37% of patients have the increased frequency of somatic mutation cells, i.e. it exceeded 95% confidence interval for the screening group. The presented results cause to anticipate that TCR-test could be used as one of criteria for formation groups of high cancer risk development.

Adult↗

PubMedDate not supplied

[RET and GFRA1 germline polymorphisms in medullary thyroid cancer patients].

The role of RET and GFRA1 germline polymorphisms in predisposition to sporadic medullary thyroid cancer (MTC) and polymorphisms' modulation effect on clinical features of inherited and sporadic MTC were investigated. Blood samples from 67 MTC patients (22 hereditary and 45 sporadic), 3 asymptomatic mutant RET gene carriers and 178 ethnically matched healthy control individuals were tested. Screening of RET exons and portion of introns 1, 8, 10, 13, 14, 15, 16 and GFRA1 5'-UTR was performed by means of direct sequencing and PCR-RFLP. 8 polymorphic variants of RET gene (exons 11, 13, 14, 15 and introns 1, 8, 13, 14) and 4 GFRA1 polymorphisms in GFRA1 were detected. Linkage disequilibrium was found between RET variants G691S and S904S, L769L and IVS8, S836S and IVS13. In sporadic MTCs, allelic frequency of only one polymorphic RET variant, L769L, was significantly decreased versus control group. In hereditary MTCs, a significant over-representation of S836S and under-representation of S904S sequence variants were observed as compared to sporadic MTCs and controls. No co-segregation was found between individual polymorphisms and phenotype of sporadic MTC. In patients with inherited MTC whose genotype was presented with polymorphic L769L and wild-type S836S, disease onset occurred 20 years later than in individuals with polymorphic L769L and S836S or wild-type L769L (p = 0.01) suggestive of a possible protective role of L769L in MTC development and modulating effect of a combination of L769L with wild-type S836S on clinical outcome of inherited MTC.

Adolescent↗

PubMedDate not supplied