Global and regional burden of colorectal cancer potentially related to Helicobacter pylori exposure: a risk attribution modelling study.

BACKGROUND: Emerging epidemiological and mechanistic studies suggest that Helicobacter pylori (H. pylori) exposure may be associated with colorectal cancer (CRC); however, the findings remain controversial. We aim to quantify the CRC burden potentially related to H. pylori exposure, with the overarching objective to inform prioritisation and future evaluation of H. pylori control as a candidate adjunct to existing CRC prevention efforts in settings with high prevalence and limited resources. METHODS: We estimated global and regional H. pylori exposure and its epidemiological association with CRC using data from systematic reviews and meta-analyses, stratified by region, diagnostic method and eradication status, among others. We derived CRC estimates from the Global Cancer Observatory (GLOBOCAN). To evaluate the related CRC burden, we calculated the estimated related proportion (ERP) with 95% uncertainty intervals (UIs) and absolute and rate-based burdens using Monte Carlo simulations. We further examined correlations between country-level ERPs, H. pylori prevalence and CRC incidence. Lasty, we used a pseudo-cohort approach to explore birth cohort-related patterns based on GLOBOCAN 2022. RESULTS: Exposure to H. pylori was associated with a 1.59-fold increased risk of CRC (95% CI 1.36 to 1.87), consistent across most subgroups. In limited observational studies, H. pylori eradication was associated with a reduced risk of CRC, but only after 10 years of follow-up. Globally, under the pooled risk-attribution model based on estimates from 43 studies, an estimated 22.0% (95% UI 14.7% to 29.4%) of CRC cases were potentially related to H. pylori exposure; corresponding estimates were lower when restricted to population-based and cohort studies (n=14). Higher H. pylori-related burdens were observed in settings with lower CRC incidence and increased with rising H. pylori prevalence. Exploratory pseudo-cohort patterns suggested higher ERPs in later birth cohorts, while absolute case counts remained relatively stable. CONCLUSION: H. pylori exposure may meaningfully contribute to global CRC burden, with the extent of preventable burden dependent on the causal nature and other modifying variables related to H. pylori exposure (eg, timing, duration). This underscores the importance of well-designed randomised clinical trials and other prospective investigations evaluating the impact of H. pylori and its eradication on CRC risk, as well as potential modifying factors.