Germline mutations in the PALB2 and CHEK2 genes and hereditary cancer

Abstract

Introduction. At least 3% of all cancer cases are associated with hereditary changes in genes predisposing to malignant neoplasms. In addition to the widely known BRCA1,2 genes, other genes involved equally with BRCA1,2 in the DNA repair system and maintenance of genome integrity, such as PALB2, CHEK2, are being introduced into routine diagnosis. In this review we present current information from recent studies on the structure and function of PALB2 and CHEK2 genes, and the diagnosis of mutations in these genes, as well as their clinical significance.The purpose of this work was to update and systematize the data on PALB2 and CHEK2 genes in order to better understand their significance in carcinogenesis, associated risks of malignant neoplasms, prevention and treatment tactics for mutation carriers.Materials and methods. PubMed, Google Scholar, Cyberleninka databases were searched. The criteria for inclusion of articles were the novelty and relevance of the data, compliance to the topic of the review. Based on this, 79 literary sources were selected.Results and discussion. Mutations in the PALB2 gene are common in 0.5 to 2.1 % of cancer cases and are associated with an increased risk of breast cancer (52.8 % by age 80), as well as ovarian cancer (5 %), pancreatic cancer (2.8 %). The frequency of changes in the CHEK2 gene reaches 5 % and is associated with a risk of breast cancer (up to 40 % by age 80) and colorectal cancer. Numerous studies have shown that mutations in these genes are associated with prostate, lung, kidney, and melanoma cancers.Conclusion. A better understanding of the spectrum of genetic predisposition and identification of genespecific cancer risks could lead to improved screening, prevention, and therapeutic strategies for patients with hereditary cancer and their families.