Helicobacter Pylori Infection is Not Causally Associated with Colorectal Cancer: A Two-Sample Mendelian Randomization Study

Abstract

Background: Some observational studies have indicated an association between Helicobacter pylori (H. pylori) infection and colorectal cancer (CRC). Nevertheless, the causal relationship between H. pylori infection and CRC remains to be evaluated.

Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate whether H. pylori infection is causally associated with CRC in the European population. We chose anti-H. pylori IgG levels as the exposure, CRC as the outcome, and genetic variants strongly linked to anti-H. pylori IgG levels (P < 1×10-5) as the instrumental variables (IVs). Data were obtained from publicly available genetic summary data, specifically the OpenGWAS database. Inverse variance weighted (IVW), weighted median, weighted mode, and MR Egger were used for MR analyses, where IVW analysis was identified as the primary method for our study. MR-Egger regression methods were used to assess horizontal pleiotropy.

Results: No causal association between anti-H. pylori IgG levels and CRC was found in IVW (β, -0.0002; 95% CI, -0.0016 to 0.0012; P = 0.7945), weighted median (β, 0.0006; 95% CI, -0.0010 to 0.0022; P = 0.4456), weighted mode (β, 0.0012; 95% CI, -0.0019 to 0.0043; P = 0.4688), and MR-Egger (β, -0.0025; 95% CI, -0.0052 to 0.0002; P = 0.0886). Sensitivity analyses did not show any evidence of heterogeneity (P = 0.1500) or horizontal pleiotropy (P = 0.0776) among the IVs.

Conclusions: H. pylori infection does not have a significant effect on the risk of CRC in the European population.

Keywords: Helicobacter pylori; Mendelian randomization; causal association; colorectal cancer.