Thai patients who fulfilled NCCN criteria for breast/ovarian cancer genetic assessment demonstrated high prevalence of germline mutations in cancer susceptibility genes: implication to Asian population testing
Open Access
- 1 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 188 (1), 237-248
- https://doi.org/10.1007/s10549-021-06152-4
Abstract
Background Germline genetic mutation plays a significant role in breast cancer susceptibility. The strength of such predisposition varies among ethnic groups across the globe, and clinical data from Asian population to develop a strategic approach to who should undergo a genetic test are lacking. Methods We performed a multigene test with next generation sequencing in Thai patients whose clinical history fulfilled NCCN criteria for breast/ovarian cancer genetic assessment, consists of 306 breast cancer patients, 62 ovarian cancer patients, 14 pancreatic cancer patients and 7 prostate cancer patients. Genetic test result and clinical history were then checked with each NCCN criteria to determined detection rate for each indication. Results There were 83 pathogenic/likely pathogenic (P/LP) variants identified in 104 patients, 44 of these P/LP variants were novel. We reported a high rate of germline P/LP variants in breast cancer (24%), ovarian cancer (37%), pancreatic cancer (14%), and prostate cancer (29%). Germline P/LP variants in BRCA1 and BRCA2 accounted for 80% of P/LP variants found in breast cancer and 57% of P/LP variants found in ovarian cancer. The detection rate of patients who fulfilled NCCN 2019 guideline for genetic/familial high-risk assessment of breast and ovarian cancers was 22–40%. Conclusion Overall, the data from this study strongly support the consideration of multigene panel test as a diagnostic tool for patients with inherited cancer susceptibility in Thailand and Asian population. Implementation of the NCCN guideline is applicable, some modification may be needed to be more suitable for Asian population.Keywords
Funding Information
- National Research Council of Thailand
- National Human Genome Research Institute
- Health Systems Research Institute
- Siriraj Core Research Facility
- Siriraj Chalermphrakiat Grant
- Thanapat Fund (D003752)
This publication has 22 references indexed in Scilit:
- Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2 Mutation Testing in Unselected General Population WomenJNCI Journal of the National Cancer Institute, 2018
- Targeted sequencing of 36 known or putative colorectal cancer susceptibility genesMolecular Genetics & Genomic Medicine, 2017
- Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testingGenetics in Medicine, 2016
- A novel start codon mutation of the MERTK gene in a patient with retinitis pigmentosa2016
- Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluationsGenetics in Medicine, 2016
- Understanding of BRCA VUS genetic results by breast cancer specialistsBMC Cancer, 2015
- Genetics of breast cancer: a topic in evolutionAnnals of Oncology, 2015
- A start codon CMT1X mutation associated with transient encephalomyelitis causes complete loss of Cx32neurogenetics, 2015
- Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular PathologyGenetics in Medicine, 2015
- Hereditary Breast Cancer: The Era of New Susceptibility GenesBioMed Research International, 2013