NDLI: Causal inference of the effect of plasma proteins on the incidence of oral cancer: two-sample Mendelian randomization

Content Provider	Springer Nature : BioMed Central
Author	Tian, Tao Li, Simin Hu, Shaonan Zhao, Yiwei Schmalz, Gerhard Acharya, Aneesha Huang, Shaohong
Abstract	Objective This study is aimed to investigate the causal relationship between plasma proteins and oral cancer risk using two-sample MR (Mendelian randomization). Methods 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. Results 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. Conclusion 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.
Related Links	https://bmcoralhealth.biomedcentral.com/counter/pdf/10.1186/s12903-024-04837-y.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	14726831
DOI	10.1186/s12903-024-04837-y
Journal	BMC Oral Health
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-09-08
Access Restriction	Open
Subject Keyword	Dentistry Oral and Maxillofacial Surgery Plasma proteins Oral cancer Two-sample Mendelian randomization Causal inference
Content Type	Text
Resource Type	Article
Subject	Dentistry
Journal Impact Factor	2.6/2023
5-Year Journal Impact Factor	3.2/2023

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