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印度尼西亚乳腺癌易感基因座的全基因组关联研究试点项目。

A pilot genome-wide association study of breast cancer susceptibility loci in Indonesia.

作者信息

Haryono Samuel J, Datasena I Gusti Bagus, Santosa Wahyu Budi, Mulyarahardja Raymond, Sari Kartika

机构信息

Department of Oncology, MRCCC Siloam Hospital Semanggi, Jakarta, Indonesia E-mail :

出版信息

Asian Pac J Cancer Prev. 2015;16(6):2231-5. doi: 10.7314/apjcp.2015.16.6.2231.

Abstract

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® 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 1.00x10(-8) and 5.00x10(-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=1.08x10(-7)]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, P=6.88x10(-6)); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, P=4.00x10(-5)); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, P=4.68x10(-5)). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.

摘要

全基因组关联研究(GWAS)为揭示乳腺癌新的遗传易感性位点提供了一种系统方法。然而,迄今为止,遗传关联研究主要在欧洲血统的女性中进行。因此,我们在此使用Affymetrix®的单核苷酸多态性(SNP)阵列5.0平台进行了一项试点GWAS,该平台包含443,813个SNP,以在89例乳腺癌病例和46名印度尼西亚血统的健康女性中寻找新的遗传风险因素。使用PLINK评估GWAS发现集的病例对照关联。使用逻辑回归分析评估等位基因和基因型关联的强度,并报告为比值比(OR)和P值;显著关联和提示性关联分别需要P值小于1.00x10(-8)和5.00x10(-5)。在分析了292,887个SNP后,我们识别出11个与乳腺癌风险具有提示性关联的染色体位点。然而,其中只有四个染色体位点有已鉴定的基因:2号染色体p.12上的CTNNA2基因[比值比(OR)=1.20,95%置信区间(CI)=1.13-1.33,P=1.08x10(-7)];18号染色体p11.2上的SOGA2基因(OR=1.32,95%CI=1.17-1.44,P=6.88x10(-6));5号染色体q14.1上的SSBP2基因(OR=1.22,95%CI=1.11-1.34,P=4.00x10(-5));以及9号染色体q31.1上的TEX10基因(OR=1.24,95%CI=1.12-1.35,P=4.68x10(-5))。本研究确定了11个染色体位点,这些位点在印度尼西亚女性中与乳腺癌风险表现出提示性关联。

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