Background And Aims: Cancer predisposition goes beyond BRCA and DNA Mismatch Repair (MMR) genes since multi-gene panel testing has become the routine diagnostic tool for hereditary cancer suspicion (HCS) cases. CHEK2 and PALB2 are some of the foremost-mutated non-BRCA/MMR actionable genes in families with a significant familial aggregation. Therefore, the purpose of this work is to unravel which tumours other than breast, ovary or colorectal display the patients.
Materials And Methods: We have analysed 528 probands that meet the inclusion criteria for Hereditary Breast and Ovarian Cancer and Lynch Syndrome established by our Hereditary Cancer Regional Program with a customized 35 genes-panel by using Ion Torrent™ Technology.
Results: We have identified pathogenic variants (PVs) in 61 families (1.55%), of which more than half (31 probands) harboured PVs in CHEK2 and PALB2 genes. Ours results reveal that not only were PVs CHEK2 and PALB2 carriers more likely to have family history of cancer not limited to breast, ovarian or colorectal cancers, but also they are prone to other extracolonic cancers, noteworthy endometrial and gastric cancers.
Conclusions: Multigene panel testing improves the chance of finding PVs in actionable genes in families with HCS. In addition, the coexistence of variants should be recorded to implement a polygenic risk algorithm that might explain the missing heritability in the aforementioned families.
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http://dx.doi.org/10.1016/j.cca.2023.117695 | DOI Listing |
Georgian Med News
October 2024
6Chitkara Centre for Research and Development, Chitkara University, Himachal Pradesh, India.
Breast cancer is a disease that has a 1 in 8 lifetime risk for women, making it an international burden. Although breast cancer mostly affects women, men have a lifetime risk of around 1 in 1000. The majority of breast cancer instances continue linked to breast cancers that have acquired somatic mutations during a person's lifespan.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
Department of Molecular Genetics and The National Tumour Biology Laboratory, National Institute of Oncology, Comprehensive Cancer Centre, Ráth György u. 7-9, 1122 Budapest, Hungary.
Using multigene panel testing for the diagnostic evaluation of patients with hereditary breast and ovarian cancer (HBOC) syndrome often identifies clinically actionable variants in genes with varying levels of penetrance. High-penetrance genes (, , , , , , ) inform specific clinical surveillance and therapeutic decisions, while recommendations for moderate-penetrance genes (, , , , , , , , , , , ) are more limited. A detailed disease history, including pedigree data, helps formulate the most appropriate and personalised management strategies.
View Article and Find Full Text PDFGenet Med Open
February 2024
Division of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA.
Purpose: As panel testing expands, more individuals with double pathogenic variants (DPVs) in cancer susceptibility genes are likely to be identified. Little is known about the effects of DPVs on cancer phenotype, although this information is crucial for genetic counseling and risk management. We sought to describe the cancer phenotype among individuals with DPVs in cancer susceptibility genes.
View Article and Find Full Text PDFGenet Med Open
February 2024
Department of Internal Medicine, University of Nevada Reno, School of Medicine, Reno, NV.
Purpose: This study aimed to evaluate the performance of different genetic screening approaches to identify women at high risk of breast cancer in the general population.
Methods: We retrospectively studied 25,591 women with available electronic health records and genetic data, participants in the Healthy Nevada Project.
Results: Family history of breast cancer was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this risk assessment method is not being properly utilized for early screening.
JCO Precis Oncol
December 2024
Divison of Cancer Genetics and Prevention, Dana-Farber Cancer Institute, Boston, MA.
Purpose: In patients with a variety of malignancies undergoing multigene panel testing (MGPT), we examined the frequency of a pathogenic/likely pathogenic variant (PV) that would not have been predicted on the basis of the patient's personal and family history of cancer.
Methods: This is a retrospective review of patients with cancer ascertained from a single academic cancer center who underwent broad-based MGPT of ≥20 cancer predisposition genes not selected on the basis of personal or family cancer history from 2015 to 2021. Low-penetrance variants and recessive inheritance genes were excluded.
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