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首页> 外文期刊>Journal of Pathology: Journal of the Pathological Society of Great Britain and Ireland >The use of Mendelian randomisation to identify causal cancer risk factors: promise and limitations
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The use of Mendelian randomisation to identify causal cancer risk factors: promise and limitations

机译：孟德尔随机化的使用来识别因果癌危险因素：承诺和局限

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Abstract The use of observational analyses, such as classical epidemiological studies or randomised controlled trials (RCTs), to infer causality in cancer may be problematic due to both ethical reasons and technical issues, such as confounding variables and reverse causation. Mendelian randomisation (MR) is an epidemiological technique that uses genetic variants as proxies for exposures in an attempt to determine whether there is a causal link between an exposure and an outcome. Given that genetic variants are randomly assigned during meiosis according to Mendel's first and second laws of heritability, MR may be thought of as a ‘natural’ RCT and is therefore less vulnerable to the aforementioned problems. MR has the potential to help identify new, and validate or disprove previously implicated, modifiable risk factors in cancer, but it is not without limitations. This review provides a brief description of the history and principles of MR, as well as a guide to basic MR methodology. The bulk of the review then examines various limitations of MR in more detail, discussing some of the proposed solutions to these problems. The review ends with a brief section detailing the practical implementation of MR, with examples of its use in the study of cancer, and an assessment of its utility in identifying cancer predisposition traits. ? 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
机译：摘要使用古典流行病学研究或随机对照试验（RCTS）的使用，以推断癌症的因果关系，可能是有问题的，因为伦理的原因和技术问题，例如混淆变量和逆转因果关系。孟德利安随机化（MR）是一种流行病学技术，它使用遗传变体作为曝光的代理，以确定是否存在曝光和结果之间存在因果关系。鉴于根据孟德尔的第一和第二级遗传法，遗传变异在减数分裂期间随机分配，MR可能被认为是“自然”RCT，因此对上述问题的影响不大。先生有可能帮助识别新的，验证和验证或反驳癌症中的含义可修改的危险因素，但并非没有限制。本综述提供了先生历史和原则的简要说明，以及基本MR方法的指南。然后，大部分审查更详细地检查了MR的各种局限性，讨论了这些问题的一些提议解决方案。审查结束于详细介绍MR的实际实施，其中关于癌症研究的用途，以及其在识别癌症易感性特征时的效用的评估。还2020作者。 John Wiley＆amp出版的病理学杂志;儿子有限公司代表大不列颠及北爱尔兰病理学协会。

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