An atlas of associations between 14 micronutrients and 22 cancer outcomes: Mendelian randomization analyses.
An atlas of associations between 14 micronutrients and 22 cancer outcomes: Mendelian randomization analyses.
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DOI：
10.1186/s12916-023-03018-y
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发表时间：
2023-08-21
期刊：
影响因子：
9.3
通讯作者：
Won, Hong-Hee
中科院分区：
文献类型：
--
作者：
Kim, Jong Yeob;Song, Minku;Kim, Min Seo;Natarajan, Pradeep;Do, Ron;Myung, Woojae;Won, Hong-Hee
微量营养素，即维生素和矿物质，与癌症结果有关；然而，它们所报道的效果在不同的研究中并不一致。我们的目的是通过应用孟德尔随机化（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，确定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，并应用双样本MR来估计它们对来自UK Biobank （UKB）和FinnGen队列（总体癌症和21种部位特异性癌症，包括乳腺癌、结直肠癌、肺癌和前列腺癌）的22种癌症结果的因果影响，此外还有来自癌症联盟的6种主要癌症结果和20种癌症亚群结果。我们使用敏感性MR方法，包括加权中位数、MR- egger和MR- presso，来评估潜在的水平多效性或异质性。欧洲血统的全基因组关联汇总统计数据用于暴露和结果数据，包括多达940,633名欧洲血统参与者，其中有133,384例癌症病例。总共进行了672次核磁共振试验（14种微量营养素× 48种癌症结果）。以下两个协会遇到Bonferroni意义关联的数量(P < 0.00016) UKB + FinnGen群体:增加乳腺癌的风险与镁水平(优势比[或]=每1 1.281标准差(SD)镁水平更高,95%可信区间[CI] = 1.151 ~ 1.426, P < 0.0001)和结肠直肠癌的风险增加维生素B12水平(或= 1.22 / 1 SD维生素B12水平更高,95% CI = 1.107 ~ 1.345, P < 0.0001)。这两种关联在癌症联合体的分析中仍然很重要。没有观察到显著的异质性或水平多效性。微量营养素水平与总体癌症风险无关。我们的研究结果可以帮助临床医生决定是否调节某些微量营养素的摄入，特别是在没有营养缺乏的高危人群中，并可能有助于设计未来的临床试验。在线版本包含补充材料，可在10.1186/s12916-023-03018-y获得。
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. The online version contains supplementary material available at 10.1186/s12916-023-03018-y.
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影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
5
作者：
Chen Z;Huang Y;Cao D;Qiu S;Chen B;Li J;Bao Y;Wei Q;Han P;Liu L
通讯作者：
Liu L
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
影响因子：
30.8
作者：
Huyghe, Jeroen R.;Bien, Stephanie A.;Peters, Ulrike
通讯作者：
Peters, Ulrike