微量营养素，即维生素和矿物质，与癌症预后有关，然而，研究结果一直存在不一致。我们旨在通过应用遗传学随机化（MR）方法，使用与微量营养素水平相关的单核苷酸多态性作为工具变量，来识别微量营养素对癌症的因果估计效应。我们获得了14种基因预测微量营养素水平的工具变量，并应用两个样本的MR方法，从英国生物库（UKB）和FinnGen队列（总癌症和21种特定部位癌症，包括乳腺癌、结直肠癌、肺癌和前列腺癌）的荟萃分析，以及癌症联合研究组织的六个主要癌症结果和20个癌症亚组结果来估计它们对22个癌症结果的因果效应。我们使用了感受性MR方法，包括带权中值、MR-Egger和MR-PRESSO，以评估潜在的水平共分叉或异质性。欧洲后裔的全基因组关联摘要统计数据被用于曝光和结果数据，包括高达940,633名欧洲后裔参与者和133,384名癌症病例。总共进行了672个MR测试（14个微量营养素×48个癌症结果）。以下两个关联在UKB加FinnGen队列中通过Bonferroni显着性（P < 0.00016）：镁水平升高与乳腺癌风险升高（比值比[OR] = 1.281，每1个标准差[SD]镁水平升高，95%置信区间[CI] = 1.151至1.426，P < 0.0001）和维生素B12水平升高与结直肠癌风险升高（OR = 1.22，每1个SD维生素B12水平升高，95% CI = 1.107至1.345，P < 0.0001）。这两个关联在癌症联合研究中仍然显著。未观察到显著的异质性或水平共分叉。微量营养素水平与总体癌症风险无关。我们的结果可能有助于临床医生决定是否调节某些微量营养素的摄入，特别是在无营养缺乏症的高风险群体，并有助于未来临床试验的设计。© 2023 BioMed Central有限公司，Springer Nature旗下。

Micronutrients, namely vitamins and minerals, are associated with cancer outcomes; however, their reported effects have been inconsistent across studies. We aimed to identify the causally estimated effects of micronutrients on cancer by applying the Mendelian randomization (MR) method, using single-nucleotide polymorphisms associated with micronutrient levels as instrumental variables.We obtained instrumental variables of 14 genetically predicted micronutrient levels and applied two-sample MR to estimate their causal effects on 22 cancer outcomes from a meta-analysis of the UK Biobank (UKB) and FinnGen cohorts (overall cancer and 21 site-specific cancers, including breast, colorectal, lung, and prostate cancer), in addition to six major cancer outcomes and 20 cancer subset outcomes from cancer consortia. We used sensitivity MR methods, including weighted median, MR-Egger, and MR-PRESSO, to assess potential horizontal pleiotropy or heterogeneity. Genome-wide association summary statistical data of European descent were used for both exposure and outcome data, including up to 940,633 participants of European descent with 133,384 cancer cases.In total, 672 MR tests (14 micronutrients × 48 cancer outcomes) were performed. The following two associations met Bonferroni significance by the number of associations (P < 0.00016) in the UKB plus FinnGen cohorts: increased risk of breast cancer with magnesium levels (odds ratio [OR] = 1.281 per 1 standard deviation [SD] higher magnesium level, 95% confidence interval [CI] = 1.151 to 1.426, P < 0.0001) and increased risk of colorectal cancer with vitamin B12 level (OR = 1.22 per 1 SD higher vitamin B12 level, 95% CI = 1.107 to 1.345, P < 0.0001). These two associations remained significant in the analysis of the cancer consortia. No significant heterogeneity or horizontal pleiotropy was observed. Micronutrient levels were not associated with overall cancer risk.Our results may aid clinicians in deciding whether to regulate the intake of certain micronutrients, particularly in high-risk groups without nutritional deficiencies, and may help in the design of future clinical trials.© 2023. BioMed Central Ltd., part of Springer Nature.