血清C反应蛋白和遗传风险在恶性肿瘤发病中的联合作用

Joint effect of serum C-reactive protein and genetic risk in the pathogenesis of cancer

目的探讨血清C反应蛋白(C-reactive protein,CRP)和遗传风险在恶性肿瘤发病中的联合作用。方法基于英国生物样本库(UK Biobank,UKB)以及前期已构建的全恶性肿瘤多基因遗传风险评分(cancer polygenic risk score,CPRS),将研究对象分为高、中、低三个遗传风险组,同时按照血清CRP浓度的自然对数值大小将研究对象分为高、中、低三个水平组。采用Cox比例风险模型,分析不同遗传风险组中,血清CRP水平与恶性肿瘤发病风险的关联。结果共纳入420940位研究对象,包括男性192942名(45.84%),女性227998名(54.16%)。血清CRP水平与多种恶性肿瘤的发病风险均存在统计学关联,随着血清CRP水平的升高,男性和女性整体恶性肿瘤的发病风险均增加(男性:HR=1.09,95%CI:1.07~1.11;女性:HR=1.09,95%CI:1.07~1.11);在低遗传风险组中,高水平CRP与恶性肿瘤发病风险关联效应更强(男性:HR=1.38;女性:HR=1.46);在高遗传风险组中,高水平CRP与恶性肿瘤发病风险关联效应较弱(男性:HR=1.07;女性:HR=1.17),呈负向交互作用。结论高血清CRP水平可增加恶性肿瘤发病风险,其在低遗传风险人群中可能具有更强的效应。

Objective To explore the joint effect of serum C-reactive protein(CRP)and genetic risk in the pathogenesis of cancer.Methods Based on UK Biobank data and the cancer polygenic risk score(CPRS)constructed previously,subjects were assigned into low,intermediate,and high genetic risk groups according to CPRS and were assigned into low,intermediate,and high groups based on natural logarithm of CRP.Cox proportional hazard model was used to test the association between serum CRP level and the risk of cancer in different genetic risk groups.Results A total of 420940 subjects including 192942(45.84%)men and 227998(54.16%)women were included.The level of serum CRP was statistically associated with the risk of multiple cancers.High level of serum CRP was associated with an increased risk of overall cancer in male and female(male:HR=1.09,95%CI:1.07-1.11;female:HR=1.09,95%CI:1.07-1.11).The effect size of CRP on cancer risk was stronger in low genetic risk group(male:HR=1.38;female:HR=1.46)compared to that of high genetic risk group(male:HR=1.07;female:HR=1.17).There was a negative interaction between CRP and genetic risk in cancer.Conclusions High level of serum CRP can increase the cancer risk.Serum CRP level may have a stronger effect in low genetic risk population.