孟德尔随机化分析在前列腺癌病因学研究中的应用现状与展望

Application status and prospect of Mendelian randomization analysis in the study of prostate cancer pathogenesis

前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤,其发病率和死亡率逐年上升,目前已成为影响男性健康的公共卫生问题。孟德尔随机化(MR)分析近年来被广泛运用于流行病学病因推断上,较一般的观察性研究避免了混杂因素干扰且因果时序清晰,其对疾病危险因素的判断更有助于疾病的早期干预和临床防治。本文综述了MR分析在前列腺癌病因学研究中的应用现状,对维生素D、端粒长度、无机盐类、睾酮水平、脂质与蛋白质、氨基酸、肠道菌群等微观暴露,以及基础疾病、药物使用、饮食因素、生活及行为习惯、青春期发育等宏观暴露与前列腺癌的因果关系进行总结,为从危险因素角度制定前列腺癌防治策略提供了依据。同时,前列腺癌领域的MR分析也具有人群分层存在偏差、数据样本量差异影响结局、纳入汇总数据时存在混杂因素、无法明确暴露影响结局的机制等不足,未来研究应当着重解决这些问题。

Prostate cancer is the most common malignant tumor of male genitourinary system,its morbidity and mortality increase year by year,and has become a public health problem affecting male health.Mendelian randomization(MR)analysis has been widely used in epidemiological etiology inference in recent years.Compared with general observational studies,it avoids the interference of confounding factors and has clear causal sequence.The judgment of disease risk factors is more helpful for early intervention and clinical prevention and treatment of diseases.This paper reviewed the application status of MR analysis in the etiology of prostate cancer,and summarized the causal relationship between the microscopic exposure of vitamin D,telomere length,inorganic salts,testosterone level,lipids and proteins,amino acids,intestinal flora,as well as the macroscopic exposure of underlying diseases,drug use,dietary factors,life and behavior habits,and adolescent development and prostate cancer.It provides the basis for formulating prevention and treatment strategy of prostate cancer from the perspective of risk factors.At the same time,MR analysis in the field of prostate cancer also has shortcomings such as bias in population stratification,difference in data sample size affecting outcome,confounding factors when incorporating aggregated data,and failure to clarify the mechanism of exposure affecting outcome.Future studies should focus on solving these problems.