Stomatological Hospital, School of Stomatology, Southern Medical University, S366 Jiangnan Boulevard, Haizhu District, Guangzhou City, 510280, Guangdong Province, China.
Department of Cariology, Endodontology and Periodontology, University of Leipzig, 04103, Leipzig, Germany.
BMC Oral Health. 2024 Sep 8;24(1):1049. doi: 10.1186/s12903-024-04837-y.
This study is aimed to investigate the causal relationship between plasma proteins and oral cancer risk using two-sample MR (Mendelian randomization).
Summary-level GWAS (genome-wide association study) data on plasma protein levels (4,907 proteins) and oral cancer (6,034 cases, 6,585 controls) of European ancestry were utilized. SNPs (single nucleotide polymorphisms) associated with proteins at genome-wide significance were selected as instrumental variables. Multiple MR methods including IVW (inverse-variance weighted), MR-Egger, weighted median, simple mode and weighted mode were applied to estimate causal effects. Sensitivity analyses were conducted.
Eight plasma proteins (CCDC167, MID2, NDRG4, PEAR1, PIAS4, RCAN1, SAMHD1 and TNMD) were identified to have significant causal associations with oral cancer risk. NDRG4, RCAN1, SAMHD1 and TNMD were associated with increased oral cancer risk while PEAR1 was associated with decreased risk. The causal estimates were consistent across different methods. Sensitivity analyses indicated the results were robust without significant heterogeneity or horizontal pleiotropy. Multivariable MR adjusting for smoking, alcohol intake and periodontal disease showed CCDC167, MID2, NDRG4, PEAR1, PIAS4 and SAMHD1 still had direct effects on oral cancer.
This two-sample MR study provides evidence for potentially causal effects of several plasma proteins on oral cancer risk. The identified proteins may serve as biomarkers and shed light on biological mechanisms underlying oral carcinogenesis. Further research is warranted to validate and extend these findings.
本研究旨在通过两样本 MR（孟德尔随机化）研究来探究血浆蛋白与口腔癌风险之间的因果关系。
本研究利用了欧洲血统人群的血浆蛋白水平（4907 种蛋白）和口腔癌（6034 例病例，6585 例对照）的全基因组关联研究汇总水平数据。选择与蛋白具有全基因组显著关联的 SNP（单核苷酸多态性）作为工具变量。采用 IVW（逆方差加权）、MR-Egger、加权中位数、简单模式和加权模式等多种 MR 方法来估计因果效应，并进行敏感性分析。
本研究共鉴定出 8 种与口腔癌风险具有显著因果关联的血浆蛋白（CCDC167、MID2、NDRG4、PEAR1、PIAS4、RCAN1、SAMHD1 和 TNMD）。NDRG4、RCAN1、SAMHD1 和 TNMD 与口腔癌风险增加相关，而 PEAR1 与风险降低相关。不同方法的因果估计结果一致。敏感性分析表明，结果稳健，无显著异质性或水平多效性。多变量 MR 调整吸烟、饮酒和牙周病后，CCDC167、MID2、NDRG4、PEAR1、PIAS4 和 SAMHD1 仍对口腔癌具有直接影响。
本两样本 MR 研究为几种血浆蛋白对口腔癌风险的潜在因果作用提供了证据。所鉴定的蛋白可能作为生物标志物，并为口腔癌发生的生物学机制提供启示。需要进一步的研究来验证和扩展这些发现。
