【摘要】 目的 评估降尿酸药物及其药物靶点与结直肠癌(colorectal cancer, CRC)发生的关联。方法 基于英国生物银行2006―2010年的数据(申请号：62663)进行前瞻性队列研究，采用倾向性评分匹配和Cox比例风险回归模型探讨降尿酸药物的使用对CRC发生风险的影响。同时采用孟德尔随机化(Mendelian randomization, MR)方法，以降尿酸药物靶基因的表达数量性状位点作为工具变量，分析3类降尿酸药物与CRC发生的关联性。结果 研究共纳入5 440名降尿酸药物使用者，年龄中位数为52.0岁，92.1%为男性，中位随访12.75年，共发生117例CRC。Cox比例风险回归模型显示，降尿酸药物使用者的CRC发生风险比未使用降尿酸药物者降低了20.2%(HR=0.798, 95%CI:0.652～0.976,P=0.029)。MR分析表明，以溶质载体家族22成员12(solute carrier family 22 member 12, SLC22A12)作为治疗靶点可以降低CRC的发生风险(OR=0.834, 95%CI:0.734～0.949,P=0.006)。结论 降尿酸药物和SLC22A12靶向的促尿酸排泄剂与CRC发生相关，为解释降尿酸药物与CRC的关联提供了可能的线索。更多还原

【Abstract】 Objective Assessing the association between uric acid-lowering drugs and their targets with the incidence of colorectal cancer(CRC). Methods Based on data from the UK Biobank from 2006 to 2010(application No: 62663), a prospective cohort study was conducted to explore the impact of uric acid-lowering drug use on the risk of CRC using propensity score matching and Cox proportional hazards model. Additionally, Mendelian randomization(MR) was employed, utilizing expression quantitative trait loci of genes targeted by uric acid-lowering drugs as instrumental variables, to analyze the associations between three types of uric acid-lowering drugs and the occurrence of CRC. Results The study included a total of 5 440 users of uric acid-lowering drugs, with a median age of 52.0 years, of whom 92.1% were male. The median follow-up period was 12.75 years, during which 117 cases of CRC were reported. The Cox proportional hazards model showed that the risk of CRC in users of uric acid-lowering drugs was reduced by 20.2% compared to non-users(HR=0.798, 95% CI: 0.652-0.976, P=0.029). MR analysis suggested that targeting solute carrier family 22 member 12(SLC22A12) may reduce the risk of CRC(OR=0.834, 95% CI: 0.734-0.949, P=0.006). Conclusions Uric acid-lowering drugs and SLC22A12-targeted uricosuric agents are associated with the occurrence of CRC, providing possible insights into explaining the relationship between uric acid-lowering drugs and CRC.更多还原