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Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history

Breast Cancer Research and Treatment volume 144, pages 635–642 (2014)Cite this article

An Erratum to this article was published on 02 April 2015

Abstract

Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.

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Acknowledgements

We thank participants for taking part in this study, all staff at the Breast Care Centre of University Malaya Medical Centre; Hanis Nazihah Hasmad, Shivaani Mariapun for assistance with sample processing, Carine Bonnard for assistance with genotyping and Ralf Moser and Darryl Irwin for assistance with genotyping assay design. This project was supported through research grants from the Malaysian Ministry of Science Technology and Innovation [10-06-06-MEB005], the Malaysian Ministry of Higher Education [University Malaya HIR Grant UM.C/HlR/MOHE/06], the Singaporean National Medical Research Council Clinician Scientist Award, the National University Cancer Institute Singapore Centre Grant Programme and charitable donations from the Cancer Research Initiatives Foundation.

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Affiliations

  1. Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia

    Peter Choon Eng Kang, Sze Yee Phuah, Kavitta Sivanandan, In Nee Kang, Eswary Thirthagiri, Norhashimah Hassan, Sook-Yee Yoon & Soo Hwang Teo

  2. Genome Institute of Singapore, Singapore, Singapore

    Jian Jun Liu

  3. Faculty of Medicine, University Malaya Cancer Research Institute, University Malaya, Kuala Lumpur, Malaysia

    Norhashimah Hassan, Nur Aishah Mohd Taib & Soo Hwang Teo

  4. Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

    Meow Keong Thong

  5. Saw Swee Hock School of Public Health and Department of Surgery, National University of Singapore, Singapore, Singapore

    Miao Hui & Mikael Hartman

  6. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Solna, Sweden

    Mikael Hartman

  7. Sime Darby Medical Centre, Subang Jaya, Malaysia

    Cheng Har Yip

  8. Department of Surgery, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia

    Cheng Har Yip & Nur Aishah Mohd Taib

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  1. Peter Choon Eng Kang
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Correspondence to Soo Hwang Teo.

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Peter Choon Eng Kang, Sze Yee Phuah, Kavitta Sivanandan and In Nee Kang are joint first authors.

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Kang, P.C.E., Phuah, S.Y., Sivanandan, K. et al. Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history. Breast Cancer Res Treat 144, 635–642 (2014). https://doi.org/10.1007/s10549-014-2894-x

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  • DOI: https://doi.org/10.1007/s10549-014-2894-x

Keywords

  • BRCA1
  • Asia
  • Recurrent
  • Breast cancer