title: Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history.
abstract: Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.
authors.affiliation: Cancer Research Initiatives Foundation, Sime Darby Medical Centre, Subang Jaya, Malaysia, peter.kang@carif.com.my.
authors.forename: Peter Choon Eng
authors.initials: PC
authors.lastname: Kang
authors.forename: Sze Yee
authors.initials: SY
authors.lastname: Phuah
authors.forename: Kavitta
authors.initials: K
authors.lastname: Sivanandan
authors.forename: In Nee
authors.initials: IN
authors.lastname: Kang
authors.forename: Eswary
authors.initials: E
authors.lastname: Thirthagiri
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Norhashimah
authors.initials: N
authors.lastname: Hassan
authors.forename: Sook-Yee
authors.initials: SY
authors.lastname: Yoon
authors.forename: Meow Keong
authors.initials: MK
authors.lastname: Thong
authors.forename: Miao
authors.initials: M
authors.lastname: Hui
authors.forename: Mikael
authors.initials: M
authors.lastname: Hartman
authors.forename: Cheng Har
authors.initials: CH
authors.lastname: Yip
authors.forename: Nur Aishah
authors.initials: NA
authors.lastname: Mohd Taib
authors.forename: Soo Hwang
authors.initials: SH
authors.lastname: Teo
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D015331:Cohort Studies; D005006:Ethnicity / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D060005:Genotyping Techniques; D006239:Haplotypes; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D012846:Singapore / Q000453:epidemiology; D055815:Young Adult