Wang Hao, Ma Keru, Shan Ming, Zhang Guoqiang
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
Eur J Nutr. 2025 Apr 5;64(4):145. doi: 10.1007/s00394-025-03663-4.
Observational studies still cannot establish a causal relationship between plasma caffeine levels and cancer risk. This study aimed to investigate the genetic effects of plasma caffeine levels on cancer risk through Mendelian randomization (MR).
Plasma caffeine's genome-wide association study (GWAS) data were derived from a meta-analysis of 9,876 individuals of European ancestry. We selected 8 single nucleotide polymorphisms (SNPs) closely associated with plasma caffeine levels as instrumental variables (IVs). The GWAS data for cancer outcomes were obtained from genotype data in the Finnish Biobank and digital health record data from the Finnish National Institute for Health and Welfare, specifically the R10 version released on December 18, 2023. The risk effects of genetic variations were assessed using the inverse variance-weighted (IVW) method and the wald ratio method.
After correction, genetically predicted higher levels of plasma caffeine were significantly associated with an increased risk of lung cancer (OR = 1.54, 95%CI: 1.33-1.78, P_FDR < 0.001). In cancer subtype analysis, genetically predicted higher levels of plasma caffeine were significantly associated with the risk of lung squamous cell carcinoma (OR = 1.60, 95%CI: 1.16-2.19, P_FDR = 0.037) and non-small cell lung cancer (OR = 1.51, 95%CI: 1.21-1.89, P_FDR = 0.003) after correction.
The current MR results indicate that long-term higher levels of plasma caffeine are associated with an increased risk of lung cancer. These findings merit further exploration to understand whether caffeine intake, supplementation, or cessation could have clinically relevant therapeutic or preventive effects.
观察性研究仍无法确定血浆咖啡因水平与癌症风险之间的因果关系。本研究旨在通过孟德尔随机化（MR）研究血浆咖啡因水平对癌症风险的遗传效应。
血浆咖啡因的全基因组关联研究（GWAS）数据来自对9876名欧洲血统个体的荟萃分析。我们选择了8个与血浆咖啡因水平密切相关的单核苷酸多态性（SNP）作为工具变量（IV）。癌症结局的GWAS数据来自芬兰生物银行的基因型数据以及芬兰国家健康与福利研究所的数字健康记录数据，具体为2023年12月18日发布的R10版本。使用逆方差加权（IVW）方法和wald比率方法评估基因变异的风险效应。
校正后，基因预测的较高血浆咖啡因水平与肺癌风险增加显著相关（OR = 1.54，95%CI：1.33 - 1.78，P_FDR < 0.001）。在癌症亚型分析中，校正后基因预测的较高血浆咖啡因水平与肺鳞状细胞癌风险（OR = 1.60，95%CI：1.16 - 2.19，P_FDR = 0.037）和非小细胞肺癌风险（OR = 1.51，95%CI：1.21 - 1.89，P_FDR = 0.003）显著相关。
当前的MR结果表明，长期较高水平的血浆咖啡因与肺癌风险增加有关。这些发现值得进一步探索，以了解咖啡因摄入、补充或戒断是否可能具有临床相关的治疗或预防作用。
