title: Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing.
abstract: Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.|University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: P S
authors.initials: PS
authors.lastname: Ng
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.|University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: W X
authors.initials: WX
authors.lastname: Wen
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
authors.forename: M Z H
authors.initials: MZ
authors.lastname: Fadlullah
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
authors.forename: S Y
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia.
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Paediatrics, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.
authors.forename: M K
authors.initials: MK
authors.lastname: Thong
authors.affiliation: Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia.
authors.forename: C H
authors.initials: CH
authors.lastname: Yip
authors.affiliation: University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia.|Department of Surgery, Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: N A
authors.initials: NA
authors.lastname: Mohd Taib
authors.affiliation: Cancer Research Malaysia, Subang Jaya, Selangor, Malaysia. soohwang.teo@cancerresearch.my.|University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia. soohwang.teo@cancerresearch.my.|Department of Surgery, Faculty of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia. soohwang.teo@cancerresearch.my.
authors.forename: S H
authors.initials: SH
authors.lastname: Teo
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics; D024682:BRCA2 Protein / Q000737:chemistry / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008296:Malaysia; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Asian; Malaysian; breast cancer; genetic testing; predisposition