Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia
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....
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BMJ Publishing Group
2017
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| author | Wen, Wei Xiong Allen, Jamie Lai, Kah Nyin Mariapun, Shivaani Hasan, Siti Norhidayu Ng, Pei Sze Lee, Daphne Shin-Chi Lee, Sheau Yee Yoon, Sook-Yee Lim, Joanna Lau, Shao Yan Decker, Brennan Pooley, Karen Dorling, Leila Luccarini, Craig Baynes, Caroline Conroy, Don M Harrington, Patricia Simard, Jacques Yip, Cheng Har Mohd Taib, Nur Aishah Ho, Weang Kee Antoniou, Antonis C Dunning, Alison M Easton, Douglas F Teo, Soo Hwang |
| author_facet | Wen, Wei Xiong Allen, Jamie Lai, Kah Nyin Mariapun, Shivaani Hasan, Siti Norhidayu Ng, Pei Sze Lee, Daphne Shin-Chi Lee, Sheau Yee Yoon, Sook-Yee Lim, Joanna Lau, Shao Yan Decker, Brennan Pooley, Karen Dorling, Leila Luccarini, Craig Baynes, Caroline Conroy, Don M Harrington, Patricia Simard, Jacques Yip, Cheng Har Mohd Taib, Nur Aishah Ho, Weang Kee Antoniou, Antonis C Dunning, Alison M Easton, Douglas F Teo, Soo Hwang |
| author_sort | Wen, Wei Xiong |
| collection | UM |
| description | 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. |
| first_indexed | 2024-03-06T05:51:02Z |
| format | Article |
| id | um.eprints-20382 |
| institution | Universiti Malaya |
| last_indexed | 2024-03-06T05:51:02Z |
| publishDate | 2017 |
| publisher | BMJ Publishing Group |
| record_format | dspace |
| spelling | um.eprints-203822019-02-18T08:36:35Z http://eprints.um.edu.my/20382/ Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia Wen, Wei Xiong Allen, Jamie Lai, Kah Nyin Mariapun, Shivaani Hasan, Siti Norhidayu Ng, Pei Sze Lee, Daphne Shin-Chi Lee, Sheau Yee Yoon, Sook-Yee Lim, Joanna Lau, Shao Yan Decker, Brennan Pooley, Karen Dorling, Leila Luccarini, Craig Baynes, Caroline Conroy, Don M Harrington, Patricia Simard, Jacques Yip, Cheng Har Mohd Taib, Nur Aishah Ho, Weang Kee Antoniou, Antonis C Dunning, Alison M Easton, Douglas F Teo, Soo Hwang R Medicine 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. BMJ Publishing Group 2017 Article PeerReviewed Wen, Wei Xiong and Allen, Jamie and Lai, Kah Nyin and Mariapun, Shivaani and Hasan, Siti Norhidayu and Ng, Pei Sze and Lee, Daphne Shin-Chi and Lee, Sheau Yee and Yoon, Sook-Yee and Lim, Joanna and Lau, Shao Yan and Decker, Brennan and Pooley, Karen and Dorling, Leila and Luccarini, Craig and Baynes, Caroline and Conroy, Don M and Harrington, Patricia and Simard, Jacques and Yip, Cheng Har and Mohd Taib, Nur Aishah and Ho, Weang Kee and Antoniou, Antonis C and Dunning, Alison M and Easton, Douglas F and Teo, Soo Hwang (2017) Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia. Journal of Medical Genetics, 55 (2). pp. 97-103. ISSN 0022-2593, DOI https://doi.org/10.1136/jmedgenet-2017-104947 <https://doi.org/10.1136/jmedgenet-2017-104947>. https://doi.org/10.1136/jmedgenet-2017-104947 doi:10.1136/jmedgenet-2017-104947 |
| spellingShingle | R Medicine Wen, Wei Xiong Allen, Jamie Lai, Kah Nyin Mariapun, Shivaani Hasan, Siti Norhidayu Ng, Pei Sze Lee, Daphne Shin-Chi Lee, Sheau Yee Yoon, Sook-Yee Lim, Joanna Lau, Shao Yan Decker, Brennan Pooley, Karen Dorling, Leila Luccarini, Craig Baynes, Caroline Conroy, Don M Harrington, Patricia Simard, Jacques Yip, Cheng Har Mohd Taib, Nur Aishah Ho, Weang Kee Antoniou, Antonis C Dunning, Alison M Easton, Douglas F Teo, Soo Hwang Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title | Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title_full | Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title_fullStr | Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title_full_unstemmed | Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title_short | Inherited mutations inBRCA1andBRCA2in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia |
| title_sort | inherited mutations inbrca1andbrca2in an unselected multiethnic cohort of asian patients with breast cancer and healthy controls from malaysia |
| topic | R Medicine |
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