Mendelian randomization in cancer research: opportunities and challenges

Mendelian Randomization (MR) is increasingly used in cancer research to infer causal relationships by leveraging genetic variants as instrumental variables. While the growth of genome-wide association studies and biobank data has expanded the utility of MR, this surge-particularly pronounced in China-raises concerns about methodological rigor. The widespread adoption may be partly driven by the Chinese translation of key MR literature. Recent advances such as multivariable MR, mediation analysis, and integration with AI and omics data have enhanced the robustness and biological interpretability of MR studies. However, challenges persist, including horizontal pleiotropy, weak instrument bias, and misinterpretation of biomarkers as causal exposures. To improve MR study credibility, frameworks like STROBE-MR and MR-GRADE are being adopted. This article reviews methodological improvements and persistent pitfalls in MR, especially within cancer epidemiology, and highlights strategies for ensuring validity in this rapidly evolving field.