biostudies-literatureUnknown14(2)Imyanitov ENHereditary cancer syndromes (HCSs) are arguably the most frequent category of Mendelian genetic diseases, as at least 2% of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants (PVs). Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity; in addition, there are several dozen less frequent types of familial tumors. The development of the majority albeit not all hereditary malignancies involves two-hit mechanism, <i>i.e.</i> the somatic inactivation of the remaining copy of the affected gene. Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes; however, population-based investigations and especially large-scale next-generation sequencing data sets demonstrate thWorld journal of clinical oncology40-68https://www.ebi.ac.uk/biostudies/studies/S-EPMC9993141biostudies-literatureHereditary cancer syndromes.PMC9993141Imyanitov ENKuligina ESSokolenko APAleksakhina SNSuspitsin ENYanus GAIyevleva AGIvantsov AOfalseHereditary cancer syndromes.Hereditary cancer syndromes (HCSs) are arguably the most frequent category of Mendelian genetic diseases, as at least 2% of presumably healthy subjects carry highly-penetrant tumor-predisposing pathogenic variants (PVs). Hereditary breast-ovarian cancer and Lynch syndrome make the highest contribution to cancer morbidity; in addition, there are several dozen less frequent types of familial tumors. The development of the majority albeit not all hereditary malignancies involves two-hit mechanism, <i>i.e.</i> the somatic inactivation of the remaining copy of the affected gene. Earlier studies on cancer families suggested nearly fatal penetrance for the majority of HCS genes; however, population-based investigations and especially large-scale next-generation sequencing data sets demonstrate th2023-01-01T00:00:00Z2023 Feb2025-04-05T13:32:27.693Z2025-02-19T04:44:14.958ZS-EPMC99931413690867710.5306/wjco.v14.i2.40