Jin Xing, Wu Mengyue, Dong Shuangshuang, Liu Hui, Ma Haochuan
Department of Laboratory Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Medical College, Yangzhou University, Yangzhou, China.
Front Nutr. 2024 Mar 6;11:1347724. doi: 10.3389/fnut.2024.1347724. eCollection 2024.
The impact of artificially sweetened beverages (ASBs) consumption on obesity-related cancers (ORCs) risk remains controversial. To address this challenging issue, this study employed wide-angle mendelian randomization (MR) analyses to explore the genetic causality between ASB consumption and the risk of ORCs, thereby effectively minimizing the impact of external confounders.
We conducted a suite of analyses encompassing univariable, multivariable, and two-step MR to evaluate causal associations between ASB consumption (samples = 85,852) and risk of ORCs (total samples = 2,974,770) using summary statistics from genome-wide association studies (GWAS). Total, direct, and intermediary effects were derived by performing inverse-variance weighted (IVW), MR-Egger, weighted mode, weighted median, and lasso method. Additionally, we performed an extensive range of sensitivity analyses to counteract the potential effects of confounders, heterogeneity, and pleiotropy, enhancing the robustness and reliability of the findings.
Genetically predicted ASB consumption was positively associated with the risk of colorectal cancer (CRC, = 0.011; OR: 6.879; 95% CI: 1.551, 30.512 by IVW) and breast cancer ( = 0.022; OR: 3.881; 95% CI: 2.023, 9.776 by IVW). Multivariable analysis yielded similar results. The results of the two-step MR unveiled that body mass index (BMI) assumes a pivotal role in mediating the association between ASB consumption and CRC risk (intermediary effect = 0.068, = 0.024).
No causal connection exists between ASB consumption and the majority of ORCs, in addition to CRC and breast cancer. Additionally, our findings suggest that BMI might be a potential mediator in the association between ASB consumption and CRC.
饮用人工甜味饮料（ASB）对肥胖相关癌症（ORC）风险的影响仍存在争议。为解决这一具有挑战性的问题，本研究采用广角孟德尔随机化（MR）分析来探讨饮用ASB与ORC风险之间的遗传因果关系，从而有效降低外部混杂因素的影响。
我们进行了一系列分析，包括单变量、多变量和两步MR分析，使用全基因组关联研究（GWAS）的汇总统计数据来评估饮用ASB（样本量 = 85,852）与ORC风险（总样本量 = 2,974,770）之间的因果关联。通过执行逆方差加权（IVW）、MR-Egger、加权模式、加权中位数和套索方法得出总效应、直接效应和中介效应。此外，我们进行了广泛的敏感性分析，以抵消混杂因素、异质性和多效性的潜在影响，增强研究结果的稳健性和可靠性。
基因预测的饮用ASB与结直肠癌（CRC，P = 0.011；比值比：6.879；95%置信区间：1.551, 30.512，采用IVW）和乳腺癌（P = 0.022；比值比：3.881；95%置信区间：2.023, 9.776，采用IVW）风险呈正相关。多变量分析得出了类似结果。两步MR分析结果表明，体重指数（BMI）在介导饮用ASB与CRC风险之间的关联中起关键作用（中介效应 = 0.068，P = 0.024）。
除CRC和乳腺癌外，饮用ASB与大多数ORC之间不存在因果关系。此外，我们的研究结果表明，BMI可能是饮用ASB与CRC之间关联的潜在中介因素。
