Association of immune cells with the risk of basal cell carcinoma: A bidirectional Mendelian randomized study

Basal cell carcinoma (BCC) is globally recognized as the most prevalent malignant skin tumor. Despite ample evidence suggesting that immune cells play a significant role in its development, the causal relationship between the 2 remains unclear. This study employed the Mendelian randomization (MR) analysis approach, utilizing publicly available genome-wide association studies data on 731 immune cell phenotypes and BCC. We primarily employ the inverse variance weighting method for our analysis, reinforced by several supplementary methodologies such as MR Egger, weighted median, simple model, and weighted model. Subsequently, we performed a comprehensive sensitivity analysis to evaluate the heterogeneity and horizontal pleiotropy effects of the findings, ensuring their robustness and reliability. According to the results of MR analysis, at a significance level of 0.01, we identified 14 immune phenotypes that were causally associated with BCC. After adjustment for multiple testing based on false discovery rate (FDR) method, 2 immune phenotypes were still significantly associated with BCC. One of them is a risk factor (PFDR < .05, odds ratio [OR] > 1), another is a protective factor (PFDR < .05, OR < 1). After reverse analysis, at a significance level of 0.01, we detected a causal relationship between BCC and 6 immune phenotypes. Four of them are positively correlated with the occurrence of BCC (P < .01, OR > 1), the other 2 are negatively correlated with the occurrence of BCC (P < .01, OR < 1). Nevertheless, after FDR correction, no statistically significant immune phenotypes were identified. The findings presented above suggest the lack of heterogeneity or horizontal pleiotropy (P > .05). In the present study, we conducted a bidirectional MR analysis to investigate the causal relationship between immune cells and BCC, unveiling the complex interaction between BCC and the immune system. In the future, the immune cells identified in this study as having a causal relationship with BCC may emerge as pivotal molecules facilitating early identification, intervention, and treatment of BCC.