Abstract
Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.
Highlights
Breast cancer is the most common cancer diagnosed among women worldwide including in Indonesia and the incidence is continuously increasing. (Akhsan and Aryandono, 2010; Jemal et al, 2011; Siegel et al, 2014) the mortality rate due to breast cancer improves during the past decades, social and economical burdens to the family and health system remain as the major problem in Indonesia
Segregation analysis studies have shown that approximately 5,10% breast and/or ovarian cancer cases are inherited with autosomal dominant pattern
Germline mutations of BRAC1 and BRCA2 genes account for the genetic predisposition and significantly increase the risk of breast and ovarian cancer
Summary
Breast cancer is the most common cancer diagnosed among women worldwide including in Indonesia and the incidence is continuously increasing. (Akhsan and Aryandono, 2010; Jemal et al, 2011; Siegel et al, 2014) the mortality rate due to breast cancer improves during the past decades, social and economical burdens to the family and health system remain as the major problem in Indonesia. Germline mutations in BRCA1 (MIM#113705; 17q chromosome) and BRCA2 (MIM#600185; 13q chromosome) genes are responsible for 25-50% of hereditary breast cancer. Women with BRCA1/2 mutations have an increased risk for breast cancer, ovarian cancer, fallopian tube cancer and other types of cancer. The risk for BRCA1-mutation carriers to develop breast cancer and ovarian cancer by age of 70 is 65-80% and 37-62%, respectively. While women with BRCA2 mutations have 45-85% and 11-23% lifetime risks to develop breast and ovarian cancer, respectively. Genetic counseling and genetic testing for BRCA1 and BRCA2 are included in the standard of care for women at high-risk for breast-ovarian cancers. To reveal prevalence of BRCA mutations in our population, we performed direct sequencing in 26 unrelated Indonesian patients with high risk of breast cancer predisposition for BRCA1/2 mutation analysis
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