Evgeny N Imyanitov, DSc, Professor, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Pesochny, Leningradskaya Str. 68, St.-Petersburg 197758, Russia. evgeny@imyanitov.spb.ru
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Feb 24, 2023; 14(2): 40-68 Published online Feb 24, 2023. doi: 10.5306/wjco.v14.i2.40
Hereditary cancer syndromes
Evgeny N Imyanitov, Ekaterina S Kuligina, Anna P Sokolenko, Evgeny N Suspitsin, Grigoriy A Yanus, Aglaya G Iyevleva, Alexandr O Ivantsov, Svetlana N Aleksakhina
Evgeny N Imyanitov, Ekaterina S Kuligina, Anna P Sokolenko, Evgeny N Suspitsin, Grigoriy A Yanus, Aglaya G Iyevleva, Alexandr O Ivantsov, Svetlana N Aleksakhina, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia
Evgeny N Imyanitov, Ekaterina S Kuligina, Anna P Sokolenko, Evgeny N Suspitsin, Grigoriy A Yanus, Aglaya G Iyevleva, Alexandr O Ivantsov, Svetlana N Aleksakhina, Department of Clinical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia
Author contributions: Imyanitov EN and Kuligina ES wrote the article draft; Kuligina ES prepared the illustration; Sokolenko AP, Suspitsin EN, Yanus GA, Iyevleva AG, Ivantsov AO, Aleksakhina SN acquired the literature data and analyzed the results; All authors approved the final version of the article.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Evgeny N Imyanitov, DSc, Professor, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Pesochny, Leningradskaya Str. 68, St.-Petersburg 197758, Russia. evgeny@imyanitov.spb.ru
Received: November 17, 2022 Peer-review started: November 17, 2022 First decision: November 30, 2022 Revised: December 9, 2022 Accepted: February 14, 2023 Article in press: February 14, 2023 Published online: February 24, 2023
Abstract
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.e. 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 that the presence of some highly-penetrant PVs is often compatible with healthy status. Hereditary cancer research initially focused mainly on cancer detection and prevention. Recent studies identified multiple HCS-specific drug vulnerabilities, which translated into the development of highly efficient therapeutic options.
Core Tip: There are many reviews describing particular types of hereditary cancer syndromes (HCSs) (e.g., hereditary breast-ovarian cancer, Lynch syndrome, Li-Fraumeni syndrome, etc.). However, for the last 15-20 years there were no publications providing a general overview on familial cancers. Our paper describes mechanisms underlying genetic cancer predisposition, lists major types of HCSs, and comments on therapeutic advances in the management of hereditary tumors.
