Effect of immune cells on hepatocellular carcinoma: a two-way Mendelian randomization study

The objective of the present study was to investigate the effect of immune cells on hepatocellular carcinoma (HCC). The GWAS Catalog database and FinnGen database were used to obtain extensive genomic data on immune cells and liver cancer. Single nucleotide polymorphisms (SNPs) associated with immune cells as instrumental variables (IV). A two-sample MR study method was used to detect the effect of immune cells on hepatocellular carcinoma. The results were analyzed using five statistical methods: inverse variance weighting (IVW), weighted median estimation, weighted model, simple model, and MR-Egger regression. In the GWASs of immune cells, 14 SNPs were selected as the instrument variables under the conditions of <italic>p</italic> &lt; 1 × 10⁻⁵, R²&lt; 0.001, physical distance &gt;10,000, and F &gt; 10. It was found that Bcells with both IgD+ and weak CD38 expression were risk factors for HCC development. The odds ratio (OR) of IgD+CD38dimB cells in HCC calculated by the IVW method was 1.346 (95% CI: 1.079−1.680; <italic>p</italic> = 0.008). The results of other MR methods were as follows: Weighted mode (OR = 1.355; 95% CI: 0.999−1.838; <italic>p</italic> = 0.072), weighted median (OR = 1.344; 95% CI: 0.972−1.858; <italic>p</italic> = 0.072). Sensitivity analysis showed that there was no heterogeneity and horizontal pleiotropy in the results. The MR analysis method showed that IgD+CD38dimB cells are risk factors for HCC.