环氧化酶-2基因启动子区多态性与结直肠癌的易感性

目的:探讨环氧化酶-2(cyclooxygenase-2,COX-2)基因启动子区的-1195(G/A,rs689466)及3’非翻译区的8473(T/C,rs5275)2个位点的基因多态性与结直肠癌(colorectal cancer,CRC)发病风险的相关性.方法:采用病例-对照研究,利用聚合酶链式反应和限制性片段长度多态性(polymerase chain reaction-restrictive fragment length polymorphism,PCR-RFLP)分析方法,对343例CRC患者和340例健康人的COX-2基因的2个位点的多态性进行检测,采用SPSS11.0软件包统计分析各位点的基因型分布和等位基因频率.结果:COX-2-8473位点多态性的各基因型频率在病例组及对照组中分布均无显著差异(P>0.05),但COX-2-1195位点多态性的基因型频率在二组中分布有显著性差异(P<0.001),结果显示CRC患者COX-2-1195AG基因型在病例组的频率较对照组显著增高(校正后OR=2.23;95%CI:1.50-3.32),AA基因型在病例组中的频率亦较对照组高(校正后OR=2.46;95%CI:1.51-4.02),A等位基因携带者在病例组中的频率高于对照组(校正后OR=2.27;95%CI:1.55-3.34).各基因型分布在结肠癌及直肠癌中的分布无显著性差异(P>0.05).COX-2-1195A等位基因与淋巴结转移及TNM分期有显著相关性.结论:COX-2-1195位点AG/AA基因型是CRC的风险因素,且与CRC的淋巴结转移及TNM分期相关.

Relationship between polymorphisms in the promoter region of the COX-2 gene and susceptibility to colorectal cancer

AIM:To investigate the correlation between polymorphisms in the promoter region(-1195G/A,rs689466) and 3’-untranslated region(8473T/C,rs5275) of the cyclooxygenase-2(COX-2) gene and risk of colorectal cancer(CRC).METHODS:A case-control study was performedin 343 patients with CRC and 340 healthy individuals.The polymerase chain reaction and restriction fragment length polymorphism(PCRRFLP) method was used to genotype the COX-21195G/A and COX-2-8473T/C polymorphisms.The SPSS 10.0 software was used to analyze genotypic and allelic frequencies.RESULTS:We found no differences in allele or genotype distributions of COX-2-8473T/C between cases and controls(all P > 0.05).However,there was an obvious difference in the polymorphism distribution of COX-2-1195G/A between the CRC group and control group(P < 0.001).Stratification analysis revealed a significantly increased risk in CRC patients carrying the AG genotype(adjusted OR = 2.23;95% CI 1.50-3.32),AA genotype(adjusted OR = 2.46;95% CI 1.51-4.02) or(AG/AA) genotype(adjusted OR = 2.27;95% CI 1.55-3.34) compared to the control group.There was no difference in the distribution of each COX-2 genotype between colon and rectal cancer.Patients carrying the COX-2-1195A allele had a higher risk of lymph node metastasis and CRC progression.CONCLUSION:COX-2-1195AG/AA genotype is associated with a higher risk of CRC,lymph node metastasis and CRC progression.