N44: Genetic And Clinical Characteristics Of Registry-Validated Pedigrees Of Lynch Syndrome Families In Slovenia – First Report

M. Krajc1, A. Blatnik1, G. Norčič2, S. Novaković3, V. Stegel3, J. Tavčar1, K. Strojnik1, V. Šetrajčič Dragoš3, G. Klančar3

1 – Cancer Genetic Clinic, Institute of Oncology Ljubljana, Slovenia. 2 – Abdominal Surgery, University CLinical Center Ljubljana, Slovenia. 3 – Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Slovenia.


Aim: The aim of this study was to assess genetic and clinical characteristics of Slovenian Lynch syndrome (LS) families, as such evaluation has not yet been performed for our population.

Method: We analyzed the results of genetic testing performed in 2008-2018 for probands fulfilling LS testing criteria. LS spectrum cancers identified in confirmed, obligate and assumed carriers of mismatch repair (MMR) gene mutations were verified in Slovenian cancer registry and analyzed according to site, age of onset, and genes involved.

Results: 25 probands out of 251 tested carried a MMR mutation. 22 different mutations, 2 of which were recurrent, were identified. Mutation detection rate was 9.9%. 48% of probands harbored MLH1, 36% MSH2, 8% MSH6 and 8% PMS2 mutations.  Of 120 cancers identified, 84 were colorectal (average age of onset: 42.2y) and 14 were endometrial carcinomas (average age of onset 52.4y).

Conclusion: We had very few referrals for LS testing in the 10-year period analyzed considering its prevalence in the population. LS is therefore likely to be drastically underdiagnosed in Slovenia. Screening of all colorectal and possibly endometrial cancers with immunohistochemical test should be performed in order to systematically identify LS families and offer them adequate treatment and familial risk assessment in the future.