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Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia
- Source :
- Breast cancer research and treatment. 165(3)
- Publication Year :
- 2017
-
Abstract
- PURPOSE: To characterize the spectrum of germline muta-tions in BRCA1, BRCA2, and PALB2 in population-based unselected breast cancer cases in an Asian population. Methods Germline DNA from 467 breast cancer patients in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated, was sequenced for the entire coding region of BRCA1; BRCA2; PALB2; Exons 6, 7, and 8 of TP53; and Exons 7 and 8 of PTEN. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants, and variants that disrupt splice site. RESULTS: We found 27 pathogenic variants (11 BRCA1, 10 BRCA2, 4 PALB2, and 2 TP53) in 34 patients, which gave a prevalence of germline mutations of 2.8, 3.23, and 0.86%for BRCA1, BRCA2, and PALB2, respectively. Compared to mutation non-carriers, BRCA1 mutation carriers were more likely to have an earlier age at onset, triple-negative subtype, and lower body mass index, whereas BRCA2 mutation carriers were more likely to have a positive family history. Mutation carrier cases had worse survival compared to non-carriers; however, the association was mostly driven by stage and tumor subtype. We also iden-tified 19 variants of unknown significance, and some of them were predicted to alter splicing or transcription factor binding sites. CONCLUSION: Our data provide insight into the genetics of breast cancer in this understudied group and suggest the need for modifying genetic testing guidelines for this population with a much younger age at diagnosis and more limited resources compared with Caucasian populations.
- Subjects :
- 0301 basic medicine
Adult
Cancer Research
endocrine system diseases
PALB2
Population
DNA Mutational Analysis
Genes, BRCA2
Genes, BRCA1
Breast Neoplasms
medicine.disease_cause
Polymorphism, Single Nucleotide
Germline
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
Breast cancer
Germline mutation
Mutation Carrier
Pregnancy
Risk Factors
Biomarkers, Tumor
Prevalence
Medicine
Humans
Genetic Predisposition to Disease
education
skin and connective tissue diseases
Alleles
Germ-Line Mutation
Genetic testing
Aged
Genetics
Aged, 80 and over
Mutation
education.field_of_study
medicine.diagnostic_test
business.industry
Malaysia
Middle Aged
medicine.disease
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Population Surveillance
Female
business
Fanconi Anemia Complementation Group N Protein
Subjects
Details
- ISSN :
- 15737217
- Volume :
- 165
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Breast cancer research and treatment
- Accession number :
- edsair.doi.dedup.....05d8ff6b38507eed539532e9698adc1f