Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort
Van Thuan Tran, Sao Trung Nguyen, Xuan Dung Pham, Thanh Hai Phan, Chu Van Nguyen, Huu Thinh Nguyen, Huu Thinh Nguyen, Huu Phuc Nguyen, Huu Phuc Nguyen, Phuong Thao Thi Doan, Lê Anh Tuấn, Bao Toan Nguyen, Thanh Xuan Jasmine, Duy Sinh Nguyen, Lưu Hồng Đăng Nguyễn, Lưu Hồng Đăng Nguyễn, Ngoc Mai Nguyen, Duy Nguyen Xuan, Vu Uyen Tran, Hue Hanh Thi Nguyen, Hue Hanh Thi Nguyen, Minh Phong Lê, Yến Nhi Nguyễn, Thanh Thuy Thi, Dinh Kiet Truong, Hung Sang Tang, Minh‐Duy Phan, Hoai‐Nghia Nguyen, Hoai‐Nghia Nguyen, Hoa Giang, Lan N. Tu
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.