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A Pilot Genome-wide Association Study of Breast Cancer Susceptibility Loci in Indonesia
Haryono, Samuel J,Datasena, I Gusti Bagus,Santosa, Wahyu Budi,Mulyarahardja, Raymond,Sari, Kartika Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6
Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from $Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than $1.00{\times}10^{-8}$ and $5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33, $P=1.08{\times}10^{-7}$]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, $P=6.88{\times}10^{-6}$); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, $P=4.00{\times}10^{-5}$); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, $P=4.68{\times}10^{-5}$). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.
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Screening of BRCA1/2 Mutations Using Direct Sequencing in Indonesian Familial Breast Cancer Cases
Anwar, Sumadi Lukman,Haryono, Samuel J,Aryandono, Teguh,Datasena, I Gusti Bagus Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4
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.
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