Helicobacter pylori Protein–Specific Antibodies and Risk of Colorectal Cancer

Abstract

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.

Prediagnostic Helicobacter pylori Antibodies and Colorectal Cancer Risk in an Elderly, Caucasian Population

“…Associations were observed for serostatus of two (of 15) antigens, but there were no dose–response associations, and chance may explain these observations given the high number of analyses performed. Our null results for overall H. pylori serostatus were consistent with other prospective studies , but we did not observe the strong, positive associations for VacA and the other antigens found by Epplein et al , including when results were stratified by subsite, cancer stage, and age at diagnosis.…”

Helicobacter pylori and Extragastric Diseases

“…Polyp formation is also influenced not only by H. pylori infection , but also by CagA positivity of the strains , even though this data has not been confirmed in all studies . Concerning pathogenic mechanisms behind the association, hypergastrinemia did not increase the risk of any colonic neoplasm , while seropositivity to any of five specific H. pylori proteins, that is, VacA, HP231, HP305, NapA, and HcpC, has been shown to be associated with a 60–80% increase in odds ratio with a specific role for VacA seropositivity, especially for early onset and late‐stage cancers .…”

Helicobacter pylori, gastric cancer and other gastrointestinal malignancies

“…Comparing the findings with previous reports, however, substantial discrepancies in seroprevalence of specific antigens such as VacA and CagA were detected, most likely due to the differences in cohort characteristics. 25,26…”