BRCA1 and BRCA2 germline mutations in Malaysian women with early-onset breast cancer without a family history.
BACKGROUND
In Asia, breast cancer is characterised by an early age of onset: In Malaysia, approximately 50% of cases occur in women under the age of 50 years. A proportion of these cases may be attributable, at least in part, to genetic components, but to date, the contribution of genetic components to breast cancer in many of Malaysia's ethnic groups has not been well-characterised.


METHODS
Given that hereditary breast carcinoma is primarily due to germline mutations in one of two breast cancer susceptibility genes, BRCA1 and BRCA2, we have characterised the spectrum of BRCA mutations in a cohort of 37 individuals with early-onset disease (<or=40 years) and no reported family history. Mutational analysis of BRCA1 and BRCA2 was conducted by full sequencing of all exons and intron-exon junctions.


CONCLUSIONS
Here, we report a total of 14 BRCA1 and 17 BRCA2 sequence alterations, of which eight are novel (3 BRCA1 and 5 BRCA2). One deleterious BRCA1 mutation and 2 deleterious BRCA2 mutations, all of which are novel mutations, were identified in 3 of 37 individuals. This represents a prevalence of 2.7% and 5.4% respectively, which is consistent with other studies in other Asian ethnic groups (4-9%).
Toh
Gaik Theng
GT
Cancer Research Initiatives Foundation (CARIF), Outpatient Centre, Subang Jaya Medical Centre, Selangor, Malaysia.
Kang
Peter
P
Lee
Sharlene S W
SS
Lee
Daphne Shin-Chi
DS
Lee
Sheau Yee
SY
Selamat
Suhaida
S
Mohd Taib
Nur Aishah
NA
Yoon
Sook-Yee
SY
Yip
Cheng Har
CH
Teo
Soo-Hwang
SH
D000328:Adult; D017668:Age of Onset; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008296:Malaysia / Q000453:epidemiology
D019313:BRCA1 Protein; D024682:BRCA2 Protein