Introduction Recent studies suggest that there might be a relationship between lower respiratory tract infections (LRTIs) and increased susceptibility to colorectal cancer (CRC). This study aims to obtain causal estimates between them and measure the mediating impact of established modifiable risk factors. Methods In this study, we employed the two‐sample Mendelian randomization (MR) approach to explore the potential link between LRTIs and CRC susceptibility. The main results were assessed through the inverse variance weighted (IVW) method, and heterogeneity and pleiotropy were evaluated using Cochrane’s Q test and MR‐Egger analysis. Moreover, to investigate potential mediating mechanisms, we conducted a two‐step MR analysis evaluating whether 731 immune phenotypes could serve as mediators in this pathway. Results IVW revealed a positive causal impact of LRTIs on CRC (odds ratio ORs = 1.098, 95% confidence interval CI: 1.002–1.203, and p = 0.045). In the two‐step MR analysis, we observed suggestively significant causal relationships between LRTIs and 38 immune phenotypes. Among the 38 immune phenotypes, IVW analysis revealed a suggestive causal effect of CD4+ T‐cell side scatter area (SSC‐A) on CRC risk. Mediation analysis estimated that SSC‐A on CD4+ T cells accounted for 10.335% (95% CI: 9.104%–11.566%) of the total effect of LRTIs on CRC. Conclusion As an exploratory study, this MR analysis suggests a potential link between LRTIs and CRC, which may partially mediate through the SSC‐A profile of CD4+ T cells.
Zhang et al. (Thu,) studied this question.