Endocrine Abstracts

Background and aims: Medullary thyroid carcinoma (MTC) occurs as a sporadic or less commonly as an inherited form which comprises multiple endocrine neoplasia (MEN) type 2A and 2B and familial MTC. Whereas over 95% of patients with MEN2 syndrome have a germline missense mutation in the RET proto-oncogene, the detection rate of germline mutations in FMTC patients is lower as well as the detection rate of somatic mutations in sporadic MTC tumor tissues. In this context, several polymorphic variants are suspected to have a function as genetic modifiers. Some studies reported these polymorphisms to be associated with increased/decreased risk of development of MTC. We focused on screening of 7 RET gene polymorphisms - A45A (exon 2), A432A (exon 7), G691S (exon 11), L769L (exon 13), S836S (exon 14), IVS14-24G/A (intron 14), S904S (exon 15) in MTC patients and compare their occurrence with controls.

Patients and methods: The cohort of MTC patients (n=302) consisted of 14 MEN2A, 8 MEN2B, 11 FMTC and 269 sporadic MTC patients, the control group comprised 205 healthy individuals. We used SNP genotyping (with TaqMan probes) and sequencing analyses to detect mutations and polymorphisms in the RET proto-oncogene.

Results: Statistical evaluation of RET SNPs alleles revealed significant difference in frequency of polymorphisms between patients with sporadic MTC and controls only for intronic polymorphism IVS14-24G/A (P=0.003). Minor allele A is under-represented in patients with sporadic MTC compared to controls and patients with inherited MTC.

Conclusion: This study contributes to the discussion about influence of polymorphisms on the development of the disease. It seems that minor allele A in intronic polymorphism IVS14-24G/A might be protective for MTC development.

Supported by grant IGA MH CR NR/9165-3 and approved by local Ethical committee.