Background Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.
Methods Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.
Results Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.
Conclusion Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.
- breast cancer
- national comprehensive cancer network
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Handling editor Constantin Polychronakos
Contributors Acquisition of data and analysis and interpretation of data: WXW, JA, KNL, SM, SNH, PSN, DS-CL, SYL, SYY, JL, SYL, BD, KP, LD, CL, CB, DC, PH, JS, CHY, NAMT, WKH, ACA and AMD. Manuscript writing: WXW and SHT. Conception and design: SHT and DFE. All authors equally contributed to the critical review and final approval of manuscript
Funding This study was funded by research grants from the Wellcome Trust (203477/Z/16/Z), Ministry of Higher Education to University Malaya (UM.C/HIR/MOHE/06), Estee Lauder Group of Companies, Cancer Research Malaysia, Cancer Research UK (C1287/A16563 to DFE, C8197/A16565 to AMD and C12292/A20861 to ACA), the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 634935 (BRIDGES) and the PERSPECTIVE project, funded from the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministère de l’Économie, de la Science et de l’Innovation du Québec through Genome Québec and the Quebec Breast Cancer Foundation. BD was supported by the Intramural Research Program of the National Human Genome Research Institute.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Medical Ethics Committee of University Malaya Medical Centre (application number: 842.9) and the Independent Ethics Committee of Sime Darby Medical Centre (application numbers: 201109.4 and 201208.1).
Provenance and peer review Not commissioned; externally peer reviewed.
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