Seo Geom Seog, Yu Ji-In, Chae Soo-Cheon, Park Won Cheol, Shin Sae Ron, Yoo Seung Taek, Choi Suck Chei, Lee Sung Hee
Genome Research Center for Immune Disorders, Wonkwang University, Iksan, Chonbuk - South Korea and Digestive Disease Research Institute, Department of Internal Medicine, Wonkwang University, Iksan, Chonbuk - South Korea.
Int J Biol Markers. 2013 Sep 27;28(3):274-9. doi: 10.5301/JBM.5000024.
Our previous work indicated that, first, the embryonic ectoderm development (EED) gene is a candidate gene associated with the pathogenesis of ulcerative colitis (UC) and, second, that the haplotypes of the EED polymorphism are one of the markers for UC susceptibility. The risk of developing colorectal cancer (CRC) increases in patients with inflammatory bowel disease.
The present study aimed at determining the association between polymorphisms in the EED gene and CRC.
Genotype analysis of EED single nucleotide polymorphisms (SNPs) was performed with high-resolution melting analysis, and the genotype and allele frequencies of the EED SNPs were compared between CRC patients and healthy controls. The haplotype frequencies of EED for multiple loci were estimated using the expectation maximization (EM) algorithm.
Our study had a power of 76.6% at a 0.05 significance level. Genotype and allele frequencies of the SNPs and haplotype frequencies of the EED gene in CRC patients were not significantly different from those in healthy controls. Only the allele frequency of g.-1850G>C in the rectal cancer (RC) patient group was significantly different from that of the control group (p=0.04). Similarly, the genotype and allelic frequencies of the EED SNPs for either tumor site (left or right) or tumor stage were not significantly different from those in healthy controls. However, our data show an association between the g.-993G>C polymorphism in the EED gene and the presence of lymph node metastasis in CRC.
These results suggest that the SNPs of the EED gene might not be associated with susceptibility to CRC. However, this study shows that the allele frequency of g.-1850G>C in the RC patient group was significantly different from that in the control group (p=0.04) and that g.-993G>C may play a role in the lymph node metastatic process of CRC.
我们之前的研究表明，其一，胚胎外胚层发育（EED）基因是与溃疡性结肠炎（UC）发病机制相关的候选基因；其二，EED基因多态性的单倍型是UC易感性的标志物之一。炎症性肠病患者患结直肠癌（CRC）的风险会增加。
本研究旨在确定EED基因多态性与CRC之间的关联。
采用高分辨率熔解分析对EED单核苷酸多态性（SNP）进行基因分型分析，并比较CRC患者与健康对照者中EED SNP的基因型和等位基因频率。使用期望最大化（EM）算法估计EED多个位点的单倍型频率。
我们的研究在0.05的显著性水平下检验效能为76.6%。CRC患者中SNP的基因型和等位基因频率以及EED基因的单倍型频率与健康对照者相比无显著差异。仅直肠癌（RC）患者组中g.-1850G>C的等位基因频率与对照组有显著差异（p = 0.04）。同样，无论肿瘤部位（左侧或右侧）或肿瘤分期如何，EED SNP的基因型和等位基因频率与健康对照者相比均无显著差异。然而，我们的数据显示EED基因中的g.-993G>C多态性与CRC中淋巴结转移的存在有关联。
这些结果表明，EED基因的SNP可能与CRC易感性无关。然而，本研究表明，RC患者组中g.-1850G>C的等位基因频率与对照组有显著差异（p = 0.04），并且g.-993G>C可能在CRC的淋巴结转移过程中起作用。
