Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

Autor:	Wen WX; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Allen J; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Lai KN; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Mariapun S; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Hasan SN; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Ng PS; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Lee DS; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Lee SY; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Yoon SY; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Lim J; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Lau SY; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia., Decker B; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.; Department of Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA., Pooley K; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Dorling L; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Luccarini C; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Baynes C; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Conroy DM; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Harrington P; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Simard J; Genomics Center, Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Quebec, Canada., Yip CH; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.; Sime Darby Medical Centre, Subang Jaya, Selangor, Malaysia., Mohd Taib NA; Faculty of Medicine, Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya, Kuala Lumpur, Malaysia.; Department of Surgery, Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia., Ho WK; Department of Applied Mathematics, Engineering, The University of Nottingham Malaysia Campus, Semenyih, Selangor, Malaysia., Antoniou AC; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Dunning AM; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Easton DF; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.; Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK., Teo SH; Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.; Faculty of Medicine, Breast Cancer Research Unit, University Malaya Cancer Research Institute, University Malaya, Kuala Lumpur, Malaysia.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2018 Feb; Vol. 55 (2), pp. 97-103. Date of Electronic Publication: 2017 Oct 09.
DOI:	10.1136/jmedgenet-2017-104947
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)
Databáze:	MEDLINE
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