Hanis Nazihah Hasmad1, Kah Nyin Lai2, Wei Xiong Wen3, Daniel Jonathan Park4, Tú Nguyen-Dumont5, Peter Choon Eng Kang6, Eswary Thirthagiri7, Mahirah Ma'som8, Boon Kiong Lim9, Melissa Southey10, Yin Ling Woo11, Soo-Hwang Teo12. 1. Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: hanis.hasmad@cancerresearch.my. 2. Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: kahnyin.lai@cancerresearch.my. 3. Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: sean.wen@cancerresearch.my. 4. Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: djp@unimelb.edu.au. 5. Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: tun@unimelb.edu.au. 6. Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: petekangchooneng@hotmail.com. 7. Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: eswary.thirthagiri@nih.gov. 8. Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: mahirahmasom@gmail.com. 9. Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: bklim@ummc.edu.my. 10. Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: msouthey@unimelb.edu.au. 11. Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: ylwoo@ummc.edu.my. 12. Cancer Research Malaysia, Subang Jaya, Malaysia; Breast Cancer Research Unit, University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: soohwang.teo@cancerresearch.my.
Abstract
OBJECTIVE: Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancer patients from a multi-ethnic cross-sectional cohort of Asian ovarian cancer patients from Malaysia. METHODS: From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancer patients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron-exon junctions and exonic sequences of BRCA1, BRCA2, PALB2 and TP53. RESULTS: BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancer patients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing. CONCLUSIONS: Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2.
OBJECTIVE: Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancerpatients from a multi-ethnic cross-sectional cohort of Asian ovarian cancerpatients from Malaysia. METHODS: From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancerpatients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron-exon junctions and exonic sequences of BRCA1, BRCA2, PALB2 and TP53. RESULTS:BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancerpatients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing. CONCLUSIONS: Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2.