Background. Medullary thyroid cancer (MTC) is a rare, endocrine tumour that occurs as part of hereditary cancer syndrome in approximately 25% of cases and develops as a sporadic form in 75%. The aim of the study was to evaluate the frequency and type of RET mutation occurrence in the Slovenian population between 1995 and 2015.Methods. A retrospective analysis of the National Cancer Registry of the Republic of Slovenia and the Registry of Patients with MTC of the Institute of Oncology in Ljubljana between 1995 and 2015 was made. The data of 143 patients with confirmed MTC and 43 healthy relatives referred to genetic counselling and testing was analyzed. Genomic DNA was isolated from peripheral blood leukocytes. Exons 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were amplified in the polymerase chain reaction (PCR). Point mutations of the RET gene were detected by single strand confirmation analysis (SSCA) and DNA sequencing. Detected mutations were confirmed by restriction enzymes.Results. A germline mutation in the RET proto-oncogene was identified in 51 individuals, 37 among them were patients with MTC, which accounts for 25.9% of all patients with MTC. Eight different germline RET mutations were found. Codons 634 and 618 were the most frequently altered codons, followed by codon 790, codon 804 and codon 918. The average crude incidence rate of MTC (between 1995 and 2015) is 0.34 per 100,000.Conclusions. We estimated that the crude incidence rate of MTC in Slovenia is 0.34 per 100,000. We discovered that 25.9% of Slovenian patients with MTC are RET mutation carriers. The most common mutations were found on codons 634 and 618.Izhodišča. Medularni rak ščitnice (MRŠ) je redek endokrini tumor, ki se v približno 25 % primerov pojavlja v družinski obliki bolezni v sklopu multiple endokrine neoplazije tipa 2, v 75 % pa je bolezen sporadična. Namen dela je bil oceniti incidenco MRŠ ter pogostost in vrsto RET-mutacij v slovenski populaciji bolnikov med letoma 1995 in 2015.Metode. Retrospektivno smo analizirali podatke Registra raka Republike Slovenije in Registra bolnikov z MRŠ Onkološkega Inštituta v Ljubljani, zbrane med letoma 1995 in 2015. Vključili smo 143 bolnikov s potrjenim MRŠ in 43 njihovih zdravih sorodnikov, ki so bili napoteni na genetsko svetovanje in testiranje. Genomsko DNK smo izolirali iz levkocitov periferne krvi. Eksone 10, 11, 13, 14, 15 in 16 RET protoonkogena smo pomnožili z verižno reakcijo s polimerazo. Točkovne mutacije RET protoonkogena smo odkrili z metodo SSCA in DNA-sekvenciranjem. Zaznane mutacije so bile potrjene z restrikcijskimi encimi.Rezultati. Zarodno mutacijo RET protoonkogena smo odkrili pri 51 osebah; med njimi je bilo 37 bolnikov z MRŠ, kar predstavlja 25,9 % vseh bolnikov z MRŠ. Odkrili smo osem različnih mutacij RET protoonkogena. Najpogosteje smo potrdili mutacijo v kodonih 634 in 618, sledili so kodoni 790, 804 in 918. Povprečna groba letna incidenčna stopnja MRŠ v Sloveniji za opazovano obdobje znaša 0,34/100.000 prebivalcev.Zaključek. Ocenjena povprečna groba letna incidenčna stopnja MRŠ v Sloveniji je bila 0,34/100.000. Poleg tega smo ugotovili, da se RET-mutacija pojavlja v naši populaciji bolnikov v 25,9 % ter da najpogosteje prizadene kodona 634 in 618
