H. Pylori Exposure and Colorectal Cancer: The Evidence Grows

Exposure to Helicobacter pylori, known for its role in gastric cancer, may also play a role in colorectal cancer (CRC), according to results from a risk-attribution modeling study.

Based on estimates from 43 studies, H. pylori exposure was associated with a 1.59-fold higher risk of CRC (95% CI 1.36-1.87), reported Shailja C. Shah, MD, MPH, of the University of California San Diego, and colleagues in eGastroenterology.

Under the pooled risk-attribution model based on estimates from the 43 studies, an estimated 22% (95% uncertainty interval [UI] 14.7-29.4) of global CRC cases were potentially related to H. pylori exposure. However, that proportion decreased to 11.9% (95% UI 0.7-22.8) when risk estimates were derived from 14 population-based and cohort studies.

In limited observational studies, eradication of H. pylori was associated with a reduced risk of CRC, but only after 10 years of follow-up.

“The findings of this study should be considered exploratory and motivational, as the true clinical implications hinge on future well-designed studies aiming to establish a causal association between H. pylori and CRC,” the authors wrote.

However, “these findings are noteworthy in the context of the clear successes of population-level H. pylori screen-and- eradicate programs for gastric cancer prevention and underscore the potential dual benefit of H. pylori eradication on CRC risk, particularly in high H. pylori prevalence and resource-constrained settings,” they added.

Because of its causal association with gastric cancer, the International Agency for Research on Cancer has categorized H. pylori as a group 1 human carcinogen. However, its role in CRC is controversial, despite a growing body of evidence supporting an association.

For example, a previous large retrospective cohort study of U.S. military veterans suggested that 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.

Even so, “to date, evidence for a clear exposure-response remains incomplete,” Shah and team noted.

Thus, the goal of their study was to “provide evidence to inform public health and research prioritization, and to guide infection-targeted cancer prevention strategies at both global and regional levels that complement and extend beyond H. pylori eradication for gastric cancer prevention,” they wrote.

They used data from systematic reviews and meta-analyses, stratified by region, diagnostic method, and eradication status, among others. Estimates of CRC cases were derived from the Global Cancer Observatory.

Estimated proportions of CRC cases related to H. pylori exposure varied when stratified by sex, age, region, and country.

When stratified by sex, women had higher estimated proportions of CRC cases potentially related to H. pylori exposure compared with men (24.8% vs 19.9%).

In addition, the proportion of CRC cases linked to H. pylori exposure was greater among those born more recently, increasing from 9.5% in those born before 1947 to 10.2% among those born in 1948 to 1962, and 15% among those born in 1963 to 1977.

The highest age-standardized incidence rates of CRC potentially related to H. pylori exposure were observed in Japan (9.0 per 100,000), Portugal (8.4 per 100,000), and South Korea (7.8 per 100,000). The age-standardized incidence rate for the U.S. was 2.5 per 100,000.

The Western Pacific and Mongolia had the highest estimated proportions of CRC cases potentially linked to H. pylori exposure (25% and 36%, respectively). While there was a similarly high prevalence of H. pylori in Africa, South-East Asia, and the Eastern Mediterranean, those regions had lower estimated proportions of CRC cases potentially attributable to H. pylori exposure.

Shah and team acknowledged that “evidence directly evaluating H. pylori eradication and subsequent CRC risk remains sparse and largely observational,” and is often limited by short follow-up and potential confounders.

“Therefore our findings should be interpreted as hypothesis-generating, and further prospective and interventional studies are needed,” they wrote.