Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Cancer Cell Int. 2014 Mar 31;14(1):29. doi: 10.1186/1475-2867-14-29.
ORAI1 channels play an important role for breast cancer progression and metastasis. Previous studies indicated the strong correlation between breast cancer and individual single nucleotide polymorphisms (SNPs) of ORAI1 gene. However, the possible SNP-SNP interaction of ORAI1 gene was not investigated.
To develop the complex analyses of SNP-SNP interaction, we propose a genetic algorithm (GA) to detect the model of breast cancer association between five SNPs (rs12320939, rs12313273, rs7135617, rs6486795 and rs712853) of ORAI1 gene. For individual SNPs, the differences between case and control groups in five SNPs of ORAI1 gene were not significant. In contrast, GA-generated SNP models show that 2-SNP (rs12320939-GT/rs6486795-CT), 3-SNP (rs12320939-GT/rs12313273-TT/rs6486795-TC), 5-SNP (rs12320939-GG/rs12313273-TC/rs7135617-TT/rs6486795-TT/rs712853-TT) have higher risks for breast cancer in terms of odds ratio analysis (1.357, 1.689, and 13.148, respectively).
Taken together, the cumulative effects of SNPs of ORAI1 gene in breast cancer association study were well demonstrated in terms of GA-generated SNP models.
ORAI1 通道在乳腺癌的进展和转移中起着重要作用。先前的研究表明乳腺癌与 ORAI1 基因的个体单核苷酸多态性(SNP)之间存在很强的相关性。然而,ORAI1 基因的 SNP-SNP 相互作用尚未被研究。
为了开发 SNP-SNP 相互作用的复杂分析,我们提出了一种遗传算法(GA)来检测 ORAI1 基因的五个 SNP(rs12320939、rs12313273、rs7135617、rs6486795 和 rs712853)与乳腺癌关联的模型。对于个体 SNP,ORAI1 基因五个 SNP 在病例组和对照组之间的差异不显著。相比之下,GA 生成的 SNP 模型显示,2-SNP(rs12320939-GT/rs6486795-CT)、3-SNP(rs12320939-GT/rs12313273-TT/rs6486795-TC)、5-SNP(rs12320939-GG/rs12313273-TC/rs7135617-TT/rs6486795-TT/rs712853-TT)在优势比分析中具有更高的乳腺癌风险(分别为 1.357、1.689 和 13.148)。
总之,GA 生成的 SNP 模型很好地证明了 ORAI1 基因 SNP 在乳腺癌关联研究中的累积效应。