AUTHOR=Tran Van Thuan , Nguyen Sao Trung , Pham Xuan Dung , Phan Thanh Hai , Nguyen Van Chu , Nguyen Huu Thinh , Nguyen Huu Phuc , Doan Phuong Thao Thi , Le Tuan Anh , Nguyen Bao Toan , Jasmine Thanh Xuan , Nguyen Duy Sinh , Nguyen Hong-Dang Luu , Nguyen Ngoc Mai , Do Duy Xuan , Tran Vu Uyen , Nguyen Hue Hanh Thi , Le Minh Phong , Nguyen Yen Nhi , Do Thanh Thuy Thi , Truong Dinh Kiet , Tang Hung Sang , Phan Minh-Duy , Nguyen Hoai-Nghia , Giang Hoa , Tu Lan N. TITLE=Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.789659 DOI=10.3389/fonc.2021.789659 ISSN=2234-943X ABSTRACT=Background

Hereditary 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.

Methods

1165 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.

Results

A 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.

Conclusion

This 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.