More Evidence Linking H. Pylori Infection to Colorectal Cancer

A history of Helicobacter pylori infection had a modest but statistically significant association with an increased risk of colorectal cancer (CRC), including fatal CRC, a large retrospective analysis showed.

Already a causative factor in gastric cancer, infection with H. pylori increased the likelihood of developing CRC by 18% and the risk of dying of CRC by 12% versus no history of the infection. Patients with infection confirmed by serologic testing had the highest risk.

Treatment of H. pylori infection reduced the risk of CRC and CRC mortality by a magnitude similar to that afforded by colonoscopy, reported Shailja C. Shah, MD, MPH, of the University of California San Diego and VA San Diego Healthcare System, and co-authors in the Journal of Clinical Oncology.

“While our data, supported by mechanistic studies, are compelling, more studies are needed to confirm the strength and consistency of these associations,” the authors wrote in conclusion. “In the interim, on the basis of the data presented herein, we posit that testing and treating for H. pylori may reduce the risk not only for gastric cancer but also for CRC.”

The findings added to evidence from observational studies implicating H. pylori in the development of CRC and showing a potentially beneficial effect of treatment for the infection, according to the authors of an accompanying editorial.

“They found a small but significant reduction in both colorectal cancer incidence and mortality among H. pylori-positive individuals who received eradication therapy, compared with H. pylori-positive individuals who did not,” wrote Julia Butt, PhD, of the German Cancer Research Center in Heidelberg, and Meira Epplein, PhD, of the Duke University Cancer Institute in Durham, North Carolina. “This specific benefit of H. pylori eradication has not been clearly demonstrated previously but is consistent with the general findings from observational studies of an increased risk of colorectal cancer among individuals with H. pylori.”

“Although the statistically significant absolute risk reduction was small, the potential impact of a feasible, noninvasive interception strategy that could reduce both gastric and colorectal cancers is incredibly potent and should be considered in clinical care for individuals at high risk for GI [gastrointestinal] cancers,” they added.

The most common chronic bacterial infection worldwide, H. pylori has a group I carcinogen designation because of its causal association with gastric cancer. Treatment of the infection has been shown to reduce the risk of gastric cancer.

Meta-analyses have suggested that H. pylori also increases the risk of CRC, but the consistency and strength of the association has varied, the authors noted in their introduction. No randomized clinical trials or observational studies have evaluated the impact of treatment on CRC incidence or mortality.

To address the gaps in evidence, Shah and colleagues conducted a retrospective cohort study among U.S. military veterans who completed H. pylori testing from 1999 through 2018 and received care through the Veterans Health Administration (VHA). Investigators excluded patients with a history of total colectomy, inflammatory bowel disease-associated colitis, or CRC.

The primary exposures were H. pylori infection status and, among H. pylori-positive individuals, receipt of guideline-recommended treatment for the infection. The primary outcome was incident CRC, as identified by the VHA Central Cancer Registry and Oncology Domain or the National Death Index (NDI). Secondary outcomes included fatal CRC as defined by NDI code.

Data analysis included 812,736 individuals, 205,178 of whom tested positive for H. pylori. The analysis showed that H. pylori-positive status was associated with an adjusted hazard ratio of 1.18 for CRC versus H. pylori-negative status (95% CI 1.12-1.24) and an adjusted hazard ratio of 1.12 for CRC mortality (95% CI 1.03-1.21). Untreated patients had a 23% higher risk of developing CRC and a 40% higher risk of CRC death.

Stratification by race and ethnicity did not significantly alter the results for CRC incidence and mortality. The impact of untreated H. pylori infection was greater among non-Hispanic Black patients (aHR 1.61, 95% CI 1.23-2.10) and Hispanic patients (aHR 1.95, 95% CI 1.21-3.14) as compared with non-Hispanic white patients (aHR 1.19, 95% CI 0.99-1.43).

Treatment for H. pylori infection led to absolute risk reductions of CRC incidence and mortality of 0.23% to 0.35%.

“To put this into context, colonoscopy is associated with a 0.84%-1.22% absolute risk reduction in incident CRC (31% relative risk reduction) and 0.15%-0.30% absolute risk reduction in fatal CRC (50% relative risk reduction) among persons completing colonoscopy for CRC screening,” the authors wrote. “H. pylori treatment is a noninvasive intervention that additionally reduces the risk of other complications, namely gastric cancer and peptic ulcer disease, further underscoring the clinical relevance of the findings presented herein.”

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