Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma
Genetic polymorphisms in the cyclooxygenase-1 and cyclooxygenase-2 genes and risk of colorectal adenoma
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DOI：
10.1007/s00384-009-0656-8
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发表时间：
2009-06-01
影响因子：
2.8
通讯作者：
Hebert, James R.
中科院分区：
文献类型：
--
作者：
Gong, Zhihong;Bostick, Roberd M.;Hebert, James R.
环氧合酶（考克斯）酶，COX 1和COX 2，是将花生四烯酸（AA）转化为与结直肠癌发生相关的胡萝卜素的关键。我们研究的目的是调查考克斯基因多态性与结直肠腺瘤风险的关系，包括单独的和与已知与炎症和AA代谢相关的暴露的相互作用。我们研究了两个启动子多态性（COX 1中的-842 A > G和COX 2中的-765 G > C）和COX 2的3 '-UTR中的两个多态性（8473 T > C和9850 A > G）与腺瘤风险的关系。在校正潜在的混杂因素后，采用多元logistic回归模型估计结直肠腺瘤的优势比（OR）和95%置信区间（CI）。总体而言，没有证据表明四种多态性与结直肠腺瘤之间存在关联。然而，我们发现COX 2 8473 T > C多态性与非甾体抗炎药（NSAID）的使用之间存在统计学显著的相互作用。（P（相互作用）= 0.03）：观察到8473 C变异等位基因的个体也经常使用NSAID的风险降低最大COX 2 8473 T > C多态性的C等位基因可能与NSAIDs相互作用，从而降低结直肠腺瘤的发病风险。
Cyclooxygenase (COX) enzymes, COX1 and COX2, are key in converting arachidonic acid (AA) into prostaglandins that have been associated with colorectal carcinogenesis. The aim of our study was to investigate associations of polymorphisms in COX genes, alone and in interaction with exposures known to be related to inflammation and AA metabolism, with risk of colorectal adenomas.In a community-, colonoscopy-based case-control study with 162 incident, sporadic colorectal adenoma cases and 211 controls, we investigated associations of two promoter polymorphisms (-842 A > G in COX1 and -765 G > C in COX2) and two polymorphisms in the 3'-UTR of COX2 (8473 T > C and 9850 A > G) with risk of adenomas. Multiple logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma after adjusting for potential confounders.Overall, there was no evidence for an association between any of the four polymorphisms and colorectal adenomas. However, we found a statistically significant interaction between the COX2 8473 T > C polymorphism and nonsteroidal anti-inflammatory drug (NSAIDs) use (P (interaction) = 0.03): The greatest reduced risk was observed for individuals with the 8473 C variant allele who also regularly used NSAIDs (OR = 0.35, 95% CI 0.16-0.75).These results suggest that the C allele of COX2 8473 T > C polymorphism may interact with NSAIDs to reduce risk for colorectal adenoma.