Georgetown-Howard University Center for Clinical and Translational Science and Department of Family Medicine, Howard University College of Medicine, Washington, USA.
Clin Transl Sci. 2012 Feb;5(1):60-4. doi: 10.1111/j.1752-8062.2011.00373.x. Epub 2012 Jan 10.
Single nucleotide polymorphisms (SNPs) in the promoter and untranslated region of cyclooxygenase (COX)-2, an inducible enzyme responsible for the synthesis of prostaglandins, have been reported to modulate the risk for many human cancers. We performed comprehensive linkage disequilibrium (LD) and haplotype analyses of 13 single nucleotide polymorphisms of the COX-2 gene and examined its susceptibility to adenoma development in 72 African American cases and 142 controls. Results revealed significant variation in LD patterns with consequence for adenoma development. Two distinct haplotype blocks were identified; one block covered the coding regions of exon 1, introns and a section of the 3'-unstranslated region (3'-UTR), whereas the second block resided solely in the 3'-UTR region. A haplotype in block 1 increased the risk of adenoma development by threefold (odds ratio [OR]= 2.9, confidence interval [CI]= 1.8-3.7, P= 0.002). Regression analysis showed, increase in copies of minor alleles of 6,064(T>C) polymorphism associated with increased odds of adenoma development by 80% (OR = 1.80, CI = 1.09-3.21, P= 0.034), 10,848(G>A) by 84% (OR = 1.84, CI = 1.05-3.23, P= 0.034) and 10,935(A>G) by 32% (OR = 1.32, CI = 1.12-3.69, P= 0.036). These results support the hypothesis that COX-2 gene might play a role in the etiology of colon cancer and warrant further investigation in other cancers. Besides, these variations should be taken into account for disease-based association studies in which the COX-2 polymorphism is considered as a candidate gene. Clin Trans Sci 2012; Volume 5: 60-64.
单核苷酸多态性（SNP）在环氧化酶（COX）-2 的启动子和非翻译区，负责前列腺素的合成的诱导酶，已被报道调节许多人类癌症的风险。我们进行了 COX-2 基因的 13 个单核苷酸多态性的全面连锁不平衡（LD）和单体型分析，并在 72 例非裔美国人和 142 例对照中检查了其对腺瘤发生的易感性。结果显示 LD 模式的显著变化对腺瘤的发展有影响。确定了两个不同的单体型块；一个块覆盖外显子 1、内含子和 3'-非翻译区（3'-UTR）的一部分的编码区，而第二个块仅位于 3'-UTR 区域。位于块 1 的单体型使腺瘤发展的风险增加三倍（比值比[OR]=2.9，置信区间[CI]=1.8-3.7，P=0.002）。回归分析显示，6,064（T>C）多态性的次要等位基因拷贝数增加与腺瘤发展的几率增加 80%（OR=1.80，CI=1.09-3.21，P=0.034），10,848（G>A）增加 84%（OR=1.84，CI=1.05-3.23，P=0.034）和 10,935（A>G）增加 32%（OR=1.32，CI=1.12-3.69，P=0.036）相关。这些结果支持 COX-2 基因可能在结肠癌的病因学中起作用的假设，并需要在其他癌症中进一步研究。此外，在 COX-2 多态性被认为是候选基因的基于疾病的关联研究中，应该考虑这些变异。Clin Trans Sci 2012；第 5 卷：60-64 页。
