Ulrich Cornelia M, Whitton John, Yu Joon-Ho, Sibert Justin, Sparks Rachel, Potter John D, Bigler Jeannette
Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):616-9. doi: 10.1158/1055-9965.EPI-04-0510.
Prostaglandin H synthase 2 (PTGS2) or cyclooxygenase-2 (COX-2) has been shown to play a key role in the regulation of inflammation, and its inhibition is associated with a reduced risk of colon cancer. The PTGS2 (COX-2) -765G > C promoter variant is located in a putative SP1 binding site and reduces PTGS2 expression. In a Minnesota-based case-control study of cases with adenomatous (n = 494) or hyperplastic polyps (n = 186) versus polyp-free controls (n = 584), we investigated the role of the PTGS2 -765G > C promoter polymorphism. Multiple logistic regression analysis was used, adjusting for age, body mass index, caloric intake, alcohol, fiber, sex, hormone use, and smoking. For colorectal adenoma, odds ratios (OR) compared with PTGS2 -765GG as reference were GC 1.00 [95% confidence interval (95% CI), 0.74-1.35] and CC 0.53 (95% CI, 0.22-1.28). For hyperplastic polyps, the comparable adjusted odds ratios were GC 0.97 (95% CI, 0.65-1.46) and CC 0.24 (95% CI, 0.05-1.11). Risk associated with the -765G > C variant differed by aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use. Among nonusers of aspirin or other NSAIDs, the CC genotype conferred a significant decrease in risk of adenoma (OR, 0.26; 95% CI, 0.07-0.89). Use of aspirin or other NSAIDs reduced risk of adenoma only among those with the -765GG (wild type) and possibly -765CG genotypes (OR, 0.66; 95% CI, 0.48-0.92 and OR, 0.64; 95% CI, 0.40-1.02, respectively). These data suggest that COX-2 expression or activity may be beneficially suppressed, and risk of colorectal polyps reduced, by aspirin or other NSAIDs in PTGS2 -765GG (wild type) individuals and by the -765 CC variant genotype in nonusers of NSAIDs.
前列腺素H合成酶2（PTGS2）或环氧化酶-2（COX-2）已被证明在炎症调节中起关键作用，抑制该酶与降低患结肠癌风险相关。PTGS2（COX-2）-765G>C启动子变体位于一个假定的SP1结合位点，会降低PTGS2的表达。在一项基于明尼苏达州的病例对照研究中，研究对象为患有腺瘤（n = 494）或增生性息肉（n = 186）的患者与无息肉对照者（n = 584），我们调查了PTGS2 -765G>C启动子多态性的作用。采用多因素logistic回归分析，并对年龄、体重指数、热量摄入、酒精、纤维、性别、激素使用情况和吸烟进行了校正。对于结直肠腺瘤，以PTGS2 -765GG为参照，GC基因型的比值比（OR）为1.00 [95%置信区间（95%CI），0.74 - 1.35]，CC基因型为0.53（95%CI，0.22 - 1.28）。对于增生性息肉，相应的校正后比值比为GC 0.97（95%CI，0.65 - 1.46）和CC 0.24（95%CI, 0.05 - 1.11）。与-765G>C变体相关的风险因是否使用阿司匹林或其他非甾体抗炎药（NSAID）而有所不同。在未使用阿司匹林或其他NSAIDs的人群中，CC基因型使腺瘤风险显著降低（OR，0.26；95%CI，0.07 - 0.89）。仅在具有-765GG（野生型）以及可能还有-765CG基因型的人群中，使用阿司匹林或其他NSAIDs可降低腺瘤风险（OR分别为0.66；95%CI，0.48 - 0.92和OR，0.64；95%CI，0.40 - 1.02）。这些数据表明，在PTGS2 -765GG（野生型）个体中，阿司匹林或其他NSAIDs可能有益地抑制COX-2的表达或活性，从而降低结直肠息肉风险；在未使用NSAIDs的人群中，-765 CC变体基因型可能也有此作用。
