Abstract
BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.
Highlights
Cancer remains the leading cause of death worldwide with 19.3 million new cases and almost 10 million deaths in 2020 [1]
We present the results of mutation profile and prevalence of pathogenic mutations from 1165 Vietnamese participants tested in the year of 2020
This study included 1165 individuals across Vietnam who were referred by physicians or self-enrolled in genetic testing at our laboratory from January to December 2020. 403 participants met the referral indications for cancer predisposition assessment in the guidelines of American College of Medical Genetics and Genomics (ACMG) and the National Society of Genetic Counselors (NSGC) [8]
Summary
Cancer remains the leading cause of death worldwide with 19.3 million new cases and almost 10 million deaths in 2020 [1]. About 5-10% of cancer cases are hereditary and result directly from hereditary cancer syndromes (HCS), a genetic predisposition to cancer due to inherited germline mutations in one or more genes [2, 3]. The most common HCS include the hereditary breast and ovarian cancer syndrome (HBOC) and hereditary colorectal cancer syndromes (HCCS). HBOC is caused by germline mutations mainly in the BRCA1 and BRCA2 genes; individuals with HBOC tend to have early onset of breast and/or ovarian cancer as well as some other types of cancer [4]. HCCS are associated with mutations in various genes and the major types include Lynch syndrome, familial adenomatous polyposis (FAP) and MUTYH-associated adenomatous polypopsis (MAP), all of which predispose affected individuals to both colorectal and extracolonic malignancies at an early age [5]. The prevalence and genetic landscape of HCS remain unknown
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