Preventive genetic screening for detection of inherited medullary thyroid carcinoma (MTC): outcome of the five years program

M Wiench, PhD, J Wloch, MD, PhD, Z Wygoda, MD, PhD, E Gubala, PhD, D Lange, MD, PhD, M Oczko, J Roskosz, MD, PhD, A Kukulska, MD, PhD, B Jarzab, MD, PhD

Dept. of Nuclear Medicine and Endocrine Oncology, Center of Oncology – Maria Sklodowska-Curie Memorial Institute, Gliwice Branch, Poland, e-mail:,

AIM: To summarize the results of primary genetic screening for inherited MTC among our population of MTC patients. METHODS: Restriction endonuclease digestion and DNA sequencing of RET exons 10, 11, 13, 14, 16 were performed in 238 MTC patients treated in our center since 1996, in >90% of cases without any preceding familiar screening with pentagastrin tests. 42 of them belonged to known MEN2 families, 196 were clinically regarded as sporadic cases. RESULTS: Among 196 apparent sporadic cases we identified 21 (10,7%) RET germline mutation carriers. Nearly half of mutations (10) were found in non-cysteine codons. The risk of inherited disease was 25% for patients aged less than 30 years at MTC diagnosis, 9,4% for age 31-45 and 5,8% for older patients. The analysis of the impact of RET polymorphisms (codon 769 and 836) on the prevalence of MTC in young age excluded their significant contribution. RET germline mutations were also identified in 22/23 of known families, in one family a clinical suspicion of inherited disease could not be confirmed by the analysis of known mutation loci. Subsequently, 127 apparent healthy relatives were investigated and 35 mutation carriers were found. However, in majority of them the evident cancer disease was already present. In 14 cases prophylactic thyreoidectomies were performed. CONCLUSIONS: The frequency of inherited disease is about 36% in the Polish population of medullary thyroid carcinoma patients with a risk of nearly 11% for apparent sporadic cancer patients and a significant contribution of mutations in non-cysteine RET codons in this subgroup.

KEY WORDS: medullary thyroid carcinoma, RET gene.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Familial and Hereditary Cancer.

This presentation was a winner in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.