COX-2基因多态性与结直肠癌发病风险的关系研究

Relationship between cyclooxygenase-2polymorphisms and colorectal cancer risk

目的探讨环氧合酶-2（COX-2）-765G〉C、-1195G〉A、8473T〉C基因多态性与结直肠癌（CRC）遗传易感性的关系，同时评估COX-2基因多态性与某些因素共同作用对CRC发病风险的影响。方法采用病例对照研究方法，入选CRC患者130例及健康非肿瘤人群120例。PCR—RFLP方法检测病例组和对照组COX-2基因的3个多态基因型，结果采用非条件logistic回归分析，用比值比（OR）及95％可信区间（C／）评估研究因素对疾病危险度的作用。结果病例组COX_2—765G〉C、-1195G〉A、8473T〉C基因型频率与对照组间的差异均无统计学意义。根据体重指数（BMI）将研究对象分层后，发现一765GG基因型与CRc发病风险的相关性具有统计学意义，与正常BMI（〈23）相比，携带-765GG基因型且超重或肥胖者（BMI≥23）惠CRC风险增高（OR=2．024，95％CI：1．089～3．760，P=0．024）。此外，还发现吸烟可增加患CRC的风险，与不吸烟人群相比，吸烟人群中的8473TT基因型携带者患CRC的风险明显增高（0R=1．938，95％CI：1．021～3．677，P=0．042）。结论虽然COX-2765G〉C、-1195G〉A、8473T〉C基因多态性与CRC遗传易感性之间没有相关性，但是携带-765GG基因型的高BMI人群或携带8473TT基因型的吸烟人群的CRC发生风险显著增高。对COX-2基因多态性位点的检测将有助于预防CRC的发生。

Objective This study was conducted to investigate the relationship between cyclooxygenase-2 （COX-2） polymorphisms （765G〉C.-1195G〉A.8473T〉C） and colorectal cancer （CRC） risk, and to assess the effect of interaction between genetic polymorphism of COX 2 and some factors on CRC risk. Methods A hospital-based case-control study was conducted involving 130 consecutively enrolled CRC patients and 120 healthy individuals without any clinical evidence of cancer. The COX-2 polymorphisms were tesed by PCR-restriction fragment length polymorphism （PCR-RFLP）. Multivariate logistic regression analysis was used to estimate odds ratio （OR） and its 95% confidence interval （CI） as a measurement of the relationship between COX-2 polymorphisms and the CRC risk. Results The genotype frequencies of -765G〉C, 1195G）〉A and 8473T〉C were not statistically different between the experimental group and the control group. Stratifying the individuals according to the body mass index （BMI）, it was found that the -765GG genotype is related to CRC risk. Compared with the normal BMI （〈23）, those overweight or obese （BMI≥233 with 765GG genotype had an increased risk of CRC （OR = 2. 024, 95%CI： 1. 089~3. 760, P = 0. 024）. Smoking can increase the risk of CRC. Compared with nonsmokers, the smokers with 8473TT genotype had an increased risk of CRC （OR = 1. 938, 95%CI： 1. 021 -3. 677, P = 0. 042）. Conclusion Although COX-2 polymorphisms-765G〉C, -1195G〉A and 8473T〉C were not related to the susceptibility of CRC, a higher BMI with-765GG genotype and smokers with 8473TT genotype appear to be related to an increased risk of CRC. The test for COX-2 polymorphisms will help to prevent CRC.