环氧化酶-2与尿苷二磷酸葡萄糖醛酸基转移酶1A6基因多态性与结肠癌风险之间无关联。
No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk.
作者信息
Thompson Cheryl-L, Plummer Sarah-J, Merkulova Alona, Cheng Iona, Tucker Thomas-C, Casey Graham, Li Li
机构信息
Department of Family Medicine, Research Division, Case Western Reserve University, 11001 Cedar Ave., Suite 306, Cleveland, Ohio 44106-7136, United States.
出版信息
World J Gastroenterol. 2009 May 14;15(18):2240-4. doi: 10.3748/wjg.15.2240.
AIM
To investigate the association of variations in the cyclooxygenase-2 (COX2) and uridine diphosphate glucuronosyltransferase 1A6 (UGT1A6) genes and non-steroidal anti-inflammatory drugs (NSAIDs) use with risk of colon cancer.
METHODS
NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly, enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGT1A6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms (SNPs) in the COX2 and UGT1A6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population controls.
RESULTS
No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk (P > 0.05), and we did not observe that these variants modify the protective effect of NSAIDs (P > 0.05). We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon adenomas.
CONCLUSION
Our study does not support a role of COX2 and UGT1A6 genetic variations in the development of colon cancer.
目的
研究环氧化酶-2（COX2）和尿苷二磷酸葡萄糖醛酸基转移酶1A6（UGT1A6）基因变异以及非甾体抗炎药（NSAIDs）的使用与结肠癌风险之间的关联。
方法
已知NSAIDs可降低结肠癌风险，其直接作用于COX2并降低其活性。流行病学研究已将COX2基因变异与结肠癌风险相关联，但其他研究未能重复这一发现。同样，UGT1A6基因中的酶已被证明可改变NSAIDs对结肠腺瘤的治疗效果。统计学显示，UGT1A6基因多态性与NSAIDs摄入相互作用，影响结肠腺瘤的发生风险，但不影响结肠癌风险。在此，我们在422例结肠癌病例和481例人群对照中，研究了COX2和UGT1A6基因中标签单核苷酸多态性（SNP）的关联及其与NSAIDs消费的相互作用对结肠癌风险的影响。
结果
两个基因中的任何一个SNP单独与结肠癌均无统计学显著关联，在我们的样本中它们也未在统计学上显著改变NSAIDs消费的保护作用。与其他研究一样，我们未能重复COX2基因变异与结肠癌风险的关联（P>0.05），并且我们未观察到这些变异改变NSAIDs的保护作用（P>0.05）。我们能够证实UGT1A6基因变异与结肠癌风险缺乏关联，尽管还需进一步研究以证实这些变异与结肠腺瘤的关联。
结论
我们的研究不支持COX2和UGT1A6基因变异在结肠癌发生中的作用。
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