No evident causal association between Helicobacter pylori infection and colorectal cancer: a bidirectional mendelian randomization study

Abstract

Observational studies have reported a correlation between Helicobacter pylori infection and colorectal cancer (CRC); however, the underlying cause has remained unclear. This research was aimed at determining whether there is a correlation between H. pylori infection and CRC by measuring the prevalence of H. pylori CagA antibodies and VacA antibodies. Using data from many genome-wide association studies (GWAS), we conducted a Mendelian randomization (MR) study with two sample GWAS. Then, we used bidirectional MR to evaluate the association between H. pylori infection and CRC for identifying causation. The most common method of analysis was the inverse variance-weighted technique. In addition, we performed supplementary analyses using the weighted median technique and MR-Egger regression. Horizontal pleiotropic outliers were identified and corrected using the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) method. Genetically predicted anti-H. pylori IgG seropositivity was not causally associated with CRC [odds ratio (OR): 1.12; 95% confidence interval (CI): 0.98-1.27, P = 0.08] and neither were H. pylori VacA antibody levels (OR = 0.96, 95% CI: 0.90-1.02, P = 0.25) or H. pylori CagA antibody levels (OR = 1.00, 95% CI: 0.93-1.07, P = 0.92). Furthermore, reverse MR analysis did not reveal evidence for a causal effect of CRC on H. pylori infection. The weighted median, the MR-Egger method, and MR-PRESSO yielded identical results. Using genetic data, MR analysis showed there was no evidence for a causal association between seroprevalence of H. pylori infection and CRC. The relationship between H. pylori infection and CRC requires further research.

Figure 1

The workflow of the bidirectional MR study on the causal relationship between H. pylori infection and CRC.

Figure 2

Estimated causal effects between H. pylori infection and CRC using different MR methods.

Figure 3

A scatter plot of the causal relationships between H. pylori and CRC using different MR methods. (A) Causal estimates for H. pylori seroprevalence on CRC. (B) Causal estimates for VacA on CRC. (C) Causal estimates for CagA on CRC. (D) Causal estimates for CRC on H. pylori infection. The slope of each line corresponds to the causal estimate for each method.