Artificial sweeteners (ASs) have been widely added to food and beverages because of their properties of low calories and sweet taste. However, whether the consumption of ASs is causally associated with cancer risk is not clear. Here, we utilized the two-sample Mendelian randomization (MR) method to study the potential causal association. Genetic variants like single-nucleotide polymorphisms (SNPs) associated with exposure (AS consumption) were extracted from a genome-wide association study (GWAS) database including 64 949 Europeans and the influence of confounding was removed. The outcome was from 98 GWAS data and included several types of cancers like lung cancer, colorectal cancer, stomach cancer, breast cancer, and so on. The exposure–outcome SNPs were harmonized and then MR analysis was performed. The inverse-variance weighted (IVW) with random effects was used as the main analytical method accompanied by four complementary methods: MR Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses consisted of heterogeneity, pleiotropy, and leave-one-out analysis. Our results demonstrated that ASs added to coffee had a positive association with high-grade and low-grade serous ovarian cancer; ASs added to tea had a positive association with oral cavity and pharyngeal cancers, but a negative association with malignant neoplasm of the bronchus and lungs. No other cancers had a genetic causal association with AS consumption. Our MR study revealed that AS consumption had no genetic causal association with major cancers. Larger MR studies or RCTs are needed to investigate small effects and support this conclusion.

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人工甜味剂与癌症风险之间的因果关系：孟德尔随机研究

人工甜味剂（AS）因其低热量和甜味的特性而被广泛添加到食品和饮料中。然而，食用 AS 是否与癌症风险存在因果关系尚不清楚。在这里，我们利用两样本孟德尔随机化（MR）方法来研究潜在的因果关联。从包括 64949 名欧洲人的全基因组关联研究 (GWAS) 数据库中提取了与暴露（AS 消耗）相关的单核苷酸多态性 (SNP) 等遗传变异，并消除了混杂的影响。结果来自 98 个 GWAS 数据，包括肺癌、结直肠癌、胃癌、乳腺癌等多种癌症。协调暴露-结果 SNP，然后进行 MR 分析。使用具有随机效应的逆方差加权（IVW）作为主要分析方法，并辅以四种补充方法：MR Egger、加权中位数、简单模式和加权模式。敏感性分析包括异质性、多效性和留一分析。我们的结果表明，咖啡中添加的 AS 与高级别和低级别浆液性卵巢癌呈正相关；茶叶中添加的AS与口腔癌和咽癌呈正相关，但与支气管和肺部的恶性肿瘤呈负相关。没有其他癌症与 AS 消费存在遗传因果关系。我们的 MR 研究表明，食用 AS 与主要癌症没有遗传因果关系。需要更大规模的 MR 研究或 RCT 来研究微小的影响并支持这一结论。