Macarthur Mairi, Sharp Linda, Hold Georgina L, Little Julian, El-Omar Emad M
Department of Medicine and Therapeutics, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1613-8. doi: 10.1158/1055-9965.EPI-04-0878.
The reduced risk of colorectal cancer associated with cyclooxygenase enzyme inhibitors, such as aspirin and other nonsteroidal anti-inflammatory drugs, strongly suggests that chronic inflammation is a key mediator in the development of colorectal cancer. This complements recent molecular evidence demonstrating an association between a number of proinflammatory genetic polymorphisms and risk of colorectal cancer. We assessed polymorphisms in the IL-1, IL-10, TNF-A, and TGF-B genes in a population-based case-control study of colorectal cancer cases (n = 264) and frequency-matched controls (n = 408) in the Northeast of Scotland and analyzed their interaction with regular aspirin use. There was no evidence of a relation between any of the individual polymorphisms, or pairs of polymorphisms, and risk of colorectal cancer. There was a significant interaction between the IL-10-592 C/A polymorphism and aspirin use (Pinteraction = 0.03). Carriers of the variant IL-10-592 (A) allele, who produce less of the anti-inflammatory cytokine interleukin-10, had a statistically significant 50% reduced risk of colorectal cancer when taking regular aspirin (odds ratio, 0.5; 95% confidence interval, 0.25-0.97), whereas risk was not reduced in carriers of the A allele who did not use aspirin, or among aspirin users with the CC genotype. It is possible that carriers of the mutant IL-10-592 allele are more likely to derive anti-inflammatory and chemopreventive benefits from aspirin in the presence of a lower production of their own endogenous anti-inflammatory interleukin-10. These results suggest that host genetics may play a role in predicting response to chemopreventive strategies. Confirmation of these findings in other populations is required.
与环氧化酶抑制剂（如阿司匹林和其他非甾体抗炎药）相关的结直肠癌风险降低，强烈表明慢性炎症是结直肠癌发生发展的关键介质。这补充了最近的分子证据，该证据表明一些促炎基因多态性与结直肠癌风险之间存在关联。我们在苏格兰东北部进行了一项基于人群的结直肠癌病例（n = 264）和频率匹配对照（n = 408）的病例对照研究，评估了白细胞介素-1（IL-1）、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-A）和转化生长因子-β（TGF-B）基因的多态性，并分析了它们与规律服用阿司匹林之间的相互作用。没有证据表明任何单个多态性或多态性对与结直肠癌风险之间存在关联。IL-10 -592 C/A多态性与阿司匹林使用之间存在显著的相互作用（P相互作用 = 0.03）。携带变异的IL-10 -592（A）等位基因的个体产生的抗炎细胞因子白细胞介素-10较少，当规律服用阿司匹林时，患结直肠癌的风险在统计学上显著降低50%（优势比，0.5；95%置信区间，0.25 - 0.97），而未使用阿司匹林的A等位基因携带者或CC基因型的阿司匹林使用者的风险并未降低。在自身内源性抗炎白细胞介素-10产生较低的情况下，携带突变的IL-10 -592等位基因的个体可能更有可能从阿司匹林中获得抗炎和化学预防益处。这些结果表明宿主遗传学可能在预测化学预防策略的反应中起作用。需要在其他人群中证实这些发现。
