Hereditary gynecological cancers (HGCs) are rare in the general population and their exact burden is unknown. In our study, we estimated the prevalence of pathogenic variants in a newly developed panel of 17 HGC-related genes in the Slovenian population by a rigorous manual classification of variants, according to the ACMG criteria, in a population of 7091 Slovenian individuals without cancer anamnesis. Secondly, we estimated the burden of women with personal and family history of cancer in a population of 1,000 Slovenian women who were treated for non-cancer-related conditions by structured personal interviewing, using a newly developed family history screening tool. We found that the burden of pathogenic variants in HGC-related genes in the Slovenian population is 2.14 %, that the Slovenian population is enriched for pathogenic variants in the BRCA1 gene and enriched or depleted in other genes, and described other unique characteristics of the Slovenian population regarding the burden of pathogenic variants in HGC-related genes. In our study population, we found that the burden of women at increased risk for HGC varies between 6.2 and 14.8 %, depending on which clinical guidelines are used. We found that a considerable proportion of Slovenian women with an increased risk for HGC remain unidentified and at the same time show interest in genetic diagnosis. The application of our results will enable better management of the Slovenian women at risk for HGC and allow easier interpretation of the variants found in the HCG-related genes in the clinical field. At the level of public health genomics, our results represent a possible first step to more effective planning of treatment and prevention of HGC, especially toward the development of population-specific screening protocols.
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