铁状态和前列腺癌因果关系的孟德尔随机化研究  

Serum iron and risk of prostate cancer:Mendelian randomization study

作　　者：谢兴 宋琼[2,7] 侯晨阳 王慧丰 蒙珊珊 梁婷婷 魏银峰 黎有成 林耀旺[4] 胡艳玲 Xie Xing;Song Qiong;Hou Chenyang;Wang Huifeng;Meng Shanshan;Liang Tingting;Wei Yinfeng;Li Youcheng;Lin Yaowang;Hu Yanling(Life Science Institutes,Guangxi Medical University,Nanning 530021,China;Center for Translational Medicine,Guangxi Medical University,Nanning 530021,China;School of Information and Management,Guangxi Medical University,Nanning 530021,China;School of Pre-Clinical Medicine,Guangxi Medical University,Nanning 530021,China;Center for Genomics and Personalized Medicine Research,Guangxi Medical University,Nanning 530021,China;Department of Clinical Laboratory,The Eighth Affiliated Hospital of Guangxi Medical University,Guigang 537137,China;Key Laboratory of Longevity and Ageing-Related Disease of Chinese Ministry of Education,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学生命科学研究院,南宁530021 [2]广西医科大学转化医学研究中心,南宁530021 [3]广西医科大学信息与管理学院,南宁530021 [4]广西医科大学基础医学院,南宁530021 [5]广西医科大学基因组与个性化医学研究中心,南宁530021 [6]广西贵港市人民医院临床检验科,贵港537138 [7]广西医科大学长寿与老年相关疾病教育部重点实验室,南宁530021

出　　处：《广西医科大学学报》2021年第4期726-733,共8页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81472414)。

摘　　要：目的:采用孟德尔随机化法探索不同铁状态(血清铁、转铁蛋白饱和度、铁蛋白和转铁蛋白)与前列腺癌(PCa)的因果关系。方法:从铁状态的全基因组关联研究中提取出与铁状态密切相关的遗传变异位点作为工具变量,进一步在the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome(PRACTICAL)consortium数据库中选出对应的遗传位点,把与血清铁、铁蛋白浓度、转铁蛋白饱和度增加和转铁蛋白浓度降低整体有关的单核苷酸多态性位点(SNP)作为传统组,与四种铁的生物标志物强相关的SNP作为自由组。使用逆方差加权法(IVW),MR-Egger回归和加权中位数法(WM)来评价铁状态与PCa之间的因果关系。结果:从全基因组关联分析的数据中得到11个SNP作为工具变量。在传统组中,铁状态与PCa存在因果关系(OR=0.879,95%CI:0.813~0.950,P=0.001)。同时,在自由组中,血清铁与PCa存在因果关系(OR=0.910,95%CI:0.833~0.995,P=0.039)。MR-Egger回归的截距接近0且无统计学意义,表明分析结果不会受遗传多效性的影响。其他三种铁的生物标记物(转铁蛋白饱和度、铁蛋白和转铁蛋白)与PCa之间无显著因果关系(均P>0.05)。结论:以SNP作为工具变量预测铁与PCa风险存在因果关系,为PCa的治疗和预防提供了证据。Objective:To evaluate the causal effect of iron states(serum iron,transferrin saturation,ferritin and transferrin)and prostate cancer using a Mendelianrandomization analysis.Methods:The genetic variants closely related to iron states from the meta-analysis of genome-wide association studies were extracted as instrumental variables,and the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome(PRACTICAL)consortium was used to select the corresponding genetic locus.Traditional instrumental variable analyses,in which only SNPs associated with increased concentrations of serum iron and ferritin,increased transferrin saturation,and decreased concentrations of transferrin were considered eligible,SNPs strongly associated with four iron biomarkers were used as liberal instrumental variable.The inverse variance weighting(IVW),MREgger regression and weighted median were all used to evaluate the causal relationship between iron states and prostate cancer.Results:Eleven single nucleotide polymorphisms(SNPs)were obtained from the data of ge-nome-wide association analysis as instrumental variables.In traditional instrumental variable analyses,MR analysis suggested that genetically determinedthe iron states were associated with prostate cancer risk with the analysis of the IVW(OR:0.879,95%CI:0.813~0.950,P=0.001),In liberal instrumental variable analyses,MR analysis suggested that genetically determined the serum iron were associated with prostate cancer risk(OR:0.910,95%CI:0.833~0.995,P=0.039).The intercept of MR-Egger regression was close to 0 and was not statistically significant,indicating that the analysis results would not be affected by genetic pleiotropy.Conclusions:Genetically predicted serum iron were associated with prostate cancer risk,suggesting that serum iron was likely to be a causal factor in the development of prostate cancer.

关 键 词：血清铁 前列腺癌 孟德尔随机化法 

分 类 号：R737.25[医药卫生—肿瘤]