title: Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: hanis.hasmad@cancerresearch.my.
authors.forename: Hanis Nazihah
authors.initials: HN
authors.lastname: Hasmad
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: kahnyin.lai@cancerresearch.my.
authors.forename: Kah Nyin
authors.initials: KN
authors.lastname: Lai
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: sean.wen@cancerresearch.my.
authors.forename: Wei Xiong
authors.initials: WX
authors.lastname: Wen
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: djp@unimelb.edu.au.
authors.forename: Daniel Jonathan
authors.initials: DJ
authors.lastname: Park
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: tun@unimelb.edu.au.
authors.forename: Tú
authors.initials: T
authors.lastname: Nguyen-Dumont
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: petekangchooneng@hotmail.com.
authors.forename: Peter Choon Eng
authors.initials: PCE
authors.lastname: Kang
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Malaysia. Electronic address: eswary.thirthagiri@nih.gov.
authors.forename: Eswary
authors.initials: E
authors.lastname: Thirthagiri
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: mahirahmasom@gmail.com.
authors.forename: Mahirah
authors.initials: M
authors.lastname: Ma'som
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: bklim@ummc.edu.my.
authors.forename: Boon Kiong
authors.initials: BK
authors.lastname: Lim
authors.affiliation: Genetic Epidemiology Laboratory, Department of Pathology, University of Melbourne, Melbourne, Australia. Electronic address: msouthey@unimelb.edu.au.
authors.forename: Melissa
authors.initials: M
authors.lastname: Southey
authors.affiliation: Department of Obstetrics and Gynaecology, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. Electronic address: ylwoo@ummc.edu.my.
authors.forename: Yin Ling
authors.initials: YL
authors.lastname: Woo
authors.affiliation: 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.
authors.forename: Soo-Hwang
authors.initials: SH
authors.lastname: Teo
mesh_terms: D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Asian; BRCA1; BRCA2; Malaysia; Ovarian cancer; Predictor of mutation