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.

中文翻译：

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孟德尔随机化用于确定因果癌症风险因素：前景和局限性。

由于道德原因和技术问题，例如混杂变量和反向因果关系，使用观察性分析（例如经典流行病学研究或随机对照试验（RCT））来推断癌症的因果关系可能会带来问题。孟德尔随机化（MR）是一种流行病学技术，使用遗传变异作为暴露的代理，以试图确定暴露与结果之间是否存在因果关系。鉴于在减数分裂过程中根据孟德尔的第一和第二遗传力定律随机分配了遗传变异，因此MR可以被认为是“天然” RCT，因此不易受到上述问题的影响。MR有潜力帮助识别癌症中新的，验证或证明先前牵涉的，可修改的危险因素，但这并非没有限制。这篇综述简要介绍了MR的历史和原理，以及有关MR基本方法的指南。然后，大部分审查将更详细地研究MR的各种局限性，并讨论一些针对这些问题的建议解决方案。这篇综述以简短的章节结尾，详细介绍了MR的实际实施，并举例说明了其在癌症研究中的应用，并评估了其在识别癌症易感性状方面的效用。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。然后，大部分审查将更详细地研究MR的各种局限性，并讨论一些针对这些问题的建议解决方案。这篇综述以简短的章节结尾，详细介绍了MR的实际实施，并举例说明了其在癌症研究中的应用，并评估了其在识别癌症易感性状方面的效用。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。然后，大部分审查将更详细地研究MR的各种局限性，并讨论一些针对这些问题的建议解决方案。这篇综述以简短的章节结尾，详细介绍了MR的实际实施，并举例说明了其在癌症研究中的应用，并评估了其在识别癌症易感性状方面的效用。©2020作者。John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版的《病理学杂志》。