Serologic Response to Helicobacter pylori Proteins Associated With Risk of Colorectal Cancer Among Diverse Populations in the United States

Abstract

Background & aims: Previous studies reported an association of the bacteria Helicobacter pylori, the primary cause of gastric cancer, and risk of colorectal cancer (CRC). However, these findings have been inconsistent, appear to vary with population characteristics, and may be specific for virulence factor VacA. To more thoroughly evaluate the potential association of H pylori antibodies with CRC risk, we assembled a large consortium of cohorts representing diverse populations in the United States.

Methods: We used H pylori multiplex serologic assays to analyze serum samples from 4063 incident cases of CRC, collected before diagnosis, and 4063 matched individuals without CRC (controls) from 10 prospective cohorts for antibody responses to 13 H pylori proteins, including virulence factors VacA and CagA. The association of seropositivity to H pylori proteins, as well as protein-specific antibody level, with odds of CRC was determined by conditional logistic regression.

Results: Overall, 40% of controls and 41% of cases were H pylori-seropositive (odds ratio [OR], 1.09; 95% CI, 0.99-1.20). H pylori VacA-specific seropositivity was associated with an 11% increased odds of CRC (OR, 1.11; 95% CI, 1.01-1.22), and this association was particularly strong among African Americans (OR, 1.45; 95% CI, 1.08-1.95). Additionally, odds of CRC increased with level of VacA antibody in the overall cohort (P = .008) and specifically among African Americans (P = .007).

Conclusions: In an analysis of a large consortium of cohorts representing diverse populations, we found serologic responses to H pylori VacA to associate with increased risk of CRC risk, particularly for African Americans. Future studies should seek to understand whether this marker is related to virulent H pylori strains carried in these populations.

Keywords: Cohort Studies; Epidemiology; Gastrointestinal Cancers.

Figure 1:. Forest plot of sero-positivity to H pylori VacA and CRC risk by race/ethnicitiy and study.

Conditional logistic regression models were applied to determine OR (diamonds) and 95% CI (horizontal lines), controls are matched to cases by study, age, sex and race/ethnicity. No values are given when total case numbers are below 20. Weight shows the contribution of each study to the number of participants per race/ethnicity in %. The vertical line at an OR of 1 serves as a reference for null association. Pos = antibody positive.