【摘要】 目的探讨二磷酸尿苷葡萄糖苷转移酶(UGT)1A7基因第1外显子3处单核苷酸多态性与国人结直肠癌(CRC)的相关性,及其在我国自然人群中的分布频率。方法采用人群为基础的成组匹配病例对照研究,以半巢式聚合酶链反应(PCR)、等位基因特异PCR和PCR-限制性内切酶片段长度多态性(RFLP)联用分析技术对140例CRC患者和280例正常对照者的UGT1A7基因型进行检测分析。结果CRC患者携带变异等位基因(~*2,~*3,~*4)频率明显高于对照组(50．0%比38．6%,P＜0．01)。CRC患者携带变异纯合基因型频率(28．6%)明显高于对照组(14．3%),差异有统计学意义(P＜0．01)。与野生型相比,变异杂合型及纯合型OR比值增高趋势有统计学意义(X~2=12．15,P＜0．01)。红烧熏炸食品摄入与CRC发病有关,与低摄人量组(≤5．40 kg/年)相比,中(≤14．35kg/年)、高(＞14．35kg/年)摄入量组风险明显增高,在中摄入量组风险增高差异有统计学意义(P＜0．05,OR=1．84,95% CI∶1．09～3．11)。以红烧熏炸、腌制食品摄人以及吸烟、饮酒状况为分层因素,分析UGT1A7基因多态性与CRC发病的相关性,仅在吸烟个体观察到有相关效应,差异有统计学意义(P＜0．05,OR=3．13,95%CI∶1．03～9．52),在饮酒个体观察到的相关效应临界于显著性水平(P=0．05,OR=2．89,95%CI∶0．99～8．46)。结论UGT1A7基因多态性与CRC的发病呈正相关关系,同时与吸烟、饮酒等环境危险因素可能存在一定的协同作用。更多还原

【Abstract】 Objective To investigate the allele frequency distribution of UDP-glucuronosyl- transferase(UGT)1A7 gene and its association with risk of colorectal cancer(CRC)in Chinese.Meth- ods One hundred and forty cases of CRC and 280 controls matching from the same follow-up cohort population established in 1989 were enrolled.The polymerase chain reaction(PCR)-based genotyping techniques including semi-nested PCR,allele-specific PCR and PCR-restriction fragment length polymor- phism(RFLP)were used for analysis of UGT1A7 polymorphism.Results The variant allele frequency in CRC cases was significantly higher than that in controls(50.0% and 38.6%,respectively).On vari- ant genotypes analysis,the frequency of variant homogenotes in CRC patients(28.6%)was also signifi- cantly higher than that in controls(14.3%),which exhibited a significant association with CRC risk(OR =2.74,95%CI:1.54～4.88).The tendency tested by likelihood ratio suggested that the increase of risk had statistical significance(χ=12.15,P=0.00).As for the environmental exposure factors,the fried or smoked-dried meat consumption was associated with CRC,and the risk increased significantly in moderate(≤14.35 kg/year)and high (＞14.35 kg/year)intake groups compared with that in low intake(≤5.40 kg/year) group (P=0.02,OR=1.84,95%CI:1.09～3.11).Stratification analysis by environmental factors found only in previous-current cigarette smoking individuals or in previous- current alcohol drinking individuals,the variants were significantly associated with CRC(OR=3.13, 95%CI:1.03～9.52,OR=2.89,95%CI:0.99～8.46,respectively).Conclusions UGT1A7 poly- morphisms was positively related with occurance of CRC,which also exerted a synergetic effects with environmental factors,cigarette smoking and alcohol consumption.更多还原