Background
There is biological plausibility as to why infection with Helicobacter pylori, the leading cause of gastric cancer, may also increase the risk of colorectal cancer, but the epidemiological findings have been inconsistent. We assessed the association of H. pylori protein-specific infection and colorectal cancer risk in the prospective cohort, the Southern Community Cohort Study.
Methods
Multiplex serology was utilized to measure antibodies to 15 H. pylori proteins in pre-diagnostic blood among 188 incident colorectal cancer cases and 370 controls matched by age, race, sex, and blood collection timing. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI).
Results
Overall H. pylori prevalence was not associated with colorectal cancer risk (OR, 1.03; 95% CI, 0.59–1.77). However, sero-positivity to any of five specific H. pylori proteins (VacA, HP231, HP305, NapA, HcpC) was associated with a significant 60 to 80% increase in odds of risk. These associations became even stronger when limited to colon cancer risk, particularly for the known H. pylori toxin VacA (OR, 2.24; 95% CI, 1.22–4.11), including a significant, positive dose-response association by VacA antibody levels in quartiles (P<0.05). Associations with VacA sero-positivity were especially strong for early onset and late stage cancers.
Conclusions
The findings raise the hypothesis that individuals with high levels of antibodies to specific H. pylori proteins may be at higher risk of colon cancer.
Impact
Further investigation of the H. pylori – colorectal cancer association is warranted to determine the possibility of protein-specific antibody levels as a risk biomarker.