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Scientists react to study exploring potential relation between global and regional burden of colorectal cancer and Helicobacter pylori exposure, as published in eGastroenerology
Dr Rosiered Brownson-Smith, Colorectal Cancer Researcher, King’s College London, said:
“This is a well-conducted piece of modelling. The researchers took an existing statistical link between H. pylori and bowel cancer risk and used it, together with global infection and cancer data, to estimate how much bowel cancer could theoretically be tied to the infection if that link turns out to be a genuine cause-and-effect relationship. That’s a big ‘if’, and it’s one the authors themselves are careful to flag.
“The headline figure, that around a fifth of the world’s bowel cancers could be linked to H. pylori, is the upper end of what this kind of calculation can produce, built on the assumption that the association is causal. When the authors repeated the sums using only the strongest-quality studies, the estimate roughly halved, to about one in nine cases, with a much wider margin of error. That drop is really important because it shows how sensitive the headline figure is to the quality of evidence feeding into it.
“The underlying association, that people exposed to H. pylori have around a 60% higher relative risk of bowel cancer, is consistent with what’s been reported before, so it isn’t a surprising or new finding in itself. But the studies behind it varied enormously in their results and were mostly the kind of study (case-control and cross-sectional) that is more vulnerable to bias than a proper long-term cohort. People who carry H. pylori also tend to differ from those who don’t in ways that independently affect cancer risk; this is what we call confounding. These differences may include things like sanitation, diet, socioeconomic circumstances, and how often they see a doctor. Importantly, no meta-analysis of this kind can fully rule that out.
“Crucially, there is still no trial showing that treating H. pylori infection actually prevents bowel cancer. The handful of studies that have looked at this only found a benefit after more than ten years of follow-up and saw nothing at all in the shorter term. This tells us either that any effect takes a long time to show up, or that something else is driving the pattern.
“None of this means the question isn’t worth asking. H. pylori is already a well-established cause of stomach cancer, and if it does turn out to meaningfully raise bowel cancer risk too, that would matter hugely for prevention. This is especially true in parts of the world where infection is common, and resources for cancer screening are limited. But this study is a careful estimate of what might be true, not proof of what is true. It’s a strong case for running the long-term trials that continue to try and answer this question.”
–COMMENTS FROM THE SPANISH SMC–
Iago Rodríguez-Lago, a gastroenterologist at the Inflammatory Bowel Disease Unit, Department of Gastroenterology, at Galdakao-Usansolo University Hospital, said:
“It is a well-designed and well-conceived study from the outset, but it is important to understand that it has not included new patients nor does it constitute a clinical trial: it is a mathematical model that combines three previously published aspects (the global prevalence of H. pylori, the risk of colorectal cancer observed in 43 studies, and the number of cases recorded by GLOBOCAN in 2022).
“The methodology applied is robust and, in some respects, innovative: simulations to account for uncertainty in the estimates, multiple sensitivity analyses and the assessment of publication bias. It is also worth noting that the authors acknowledge that their results are exploratory, precisely because causality cannot be proven with this study design.
“Part of this limitation stems from the data source, as, of the 43 studies, 38 are case-control or cross-sectional studies, and only five are prospective cohorts. The disparity between them is very great, and the authors are barely able to account for 7 per cent of the differences (heterogeneity). In summary, the study presents a very interesting statistical model, but one based on somewhat weak evidence. Nevertheless, this approach allows for the inclusion of a very large number of patients, requires less time to obtain results, and serves to guide future research, although it does not appear likely to change our current clinical practice.
“It is consistent with what we already know, as the association was described years ago with similar magnitudes; there is a certain degree of biological plausibility, because in animal models the infection alters gut immunity and the microbiota, and eradication prevents this effect. The key to interpreting the study is to distinguish between three things: ‘association’ does not mean ‘caused’, and ‘caused’ does not mean ‘preventable’. That 22 per cent risk would only translate into preventable cases if the relationship were causal and if eradicating the bacterium were to reverse the risk. The evidence on eradication cited in the article itself is limited: four studies, with an overall neutral result, and the only indication of a benefit appears more than 10 years later. It is also worth putting these data into perspective, as in colorectal cancer, lifestyle factors, diet, family history, etc., account for a significant proportion of cases; consequently, these are still currently regarded as the key areas for preventive action.
“Although the study offers an interesting approach and a broad perspective on these issues, it does not provide any immediate practical implications for our patients or the general population. Nevertheless, it raises an interesting point, as there is therefore the possibility of a dual benefit in countries that already carry out active screening for the bacterium to prevent gastric cancer. In Spain, the priority remains increasing take-up of bowel screening, which does have a proven benefit.
“[Regarding possible limitations] If we analyse the methods used in detail, it has been mathematically assumed that the relationship between the two factors (H. pylori and colorectal cancer) is causal. We must bear in mind that the infection is also a marker of socio-economic conditions and hygiene during childhood, which are in turn linked to diet, smoking, obesity, etc.
“As some of these factors are associated with both conditions, there may be some uncertainty regarding the nature of the relationship between them and the role played by exposure to the bacterium itself.
“They also highlight a striking detail: if the bacterium were a more direct cause of the tumour, one would expect a higher risk with the more virulent strains, yet the opposite is true. All estimates for strains carrying CagA, VacA and GroEL fall below the overall risk.
“In conclusion, although one-fifth of cases are linked to the bacterium, this does not mean that one-fifth are preventable. Association does not imply causation, and causation does not imply preventability. The study shows that the higher the quality of the research from which the data is derived, the lower the observed effect. Taking all 14 studies into account, the figure drops from 22 per cent to 12 per cent, demonstrating that data quality is essential for drawing robust conclusions. Based on this evidence, we do not have sufficient grounds to screen for H. pylori with a view to reducing the risk of colorectal cancer.
“What we do know works—and with very solid evidence—is participation in colorectal cancer screening programmes. The most valuable aspect of this work is that it highlights where further research is needed, particularly in countries that already screen for the bacterium to prevent gastric cancer, as this could help us uncover the influence this might have on colorectal cancer.”
Ramón Salazar, Head of Medical Oncology at the Catalan Institute of Oncology (ICO), Head of the Colorectal Cancer Research Group, Oncobell programme (IDIBELL) and Associate Professor of Medicine at the University of Barcelona, said:
“Although the quality of data collection is high, this is a rather heterogeneous observational study in terms of the origin and nature of its databases.
“I was unaware of the proposed link between Helicobacter pylori infection and colorectal cancer, but it may make sense if the bacterium is identified in the colon, given its pro-inflammatory capacity; however, in this study it has only been quantified or detected in the stomach.
”The study finds an association between Helicobacter pylori (detected only in the stomach) and colorectal cancer, but that does not mean it has been proven that the bacterium is the cause of these tumours. Furthermore, the fact that the bacterium was detected in the stomach does not necessarily imply its presence in the colon mucosa – where it could indeed cause a pro-carcinogenic inflammatory reaction – and the strength of the correlation varies substantially depending on which studies are taken into account, suggesting that the result is not particularly robust.
“This is one of the major problems with causal inference: coincidence is not causation. As Nassim Nicholas Taleb argues in his book Fooled by Randomness, we can construct highly convincing narratives based on associations that actually reflect chance, biases or factors we have not taken into account. In science, finding an association is only the beginning; there must then be a rational mechanism of action to explain causality, and this must ultimately be validated: the difficult part is proving that we are not being misled by chance.
“In summary, although the study is well-conducted and the authors attempt to verify their results in various ways, it still relies on observational data, studies that differ significantly from one another, potential errors in measuring exposure to H. pylori, and several assumptions inherent to the model itself. For this reason, its results should be viewed as exploratory and hypothesis-generating, not as a definitive demonstration of causality.”
Luis Bujanda, a specialist in the Digestive System at Donostia University Hospital, coordinator of the Liver and Gastrointestinal Diseases Unit at the Biogipuzkoa Institute and Professor of Medicine at the University of the Basque Country (UPV/EHU), said:
“This is not a high-quality article, as it is a summary of summaries.
“[Regarding the evidence that was already known] There have been articles in favour and others against.
In general, the conclusions are unreliable and run contrary to compelling data:
The prevalence of H. pylori infection in Spain has fallen, as has gastric cancer. However, the incidence of colorectal cancer has risen.
The prevalence of H. pylori infection is the same in men as in women. However, colorectal cancer is more common in men (60 per cent of cases).”
‘Global and regional burden of colorectal cancer potentially related to Helicobacter pylori exposure: a risk attribution modelling study’ by Yunhao Li, et al. was published in eGastroenterology at 23:30 UK time Tuesday 8 September 2026
DOI: 10.1136/egastro-2026-100436
Declared interests
Iago Rodríguez-Lago: He declares no conflicts of interest.
Ramón Salazar: He declares no conflicts of interest.
Luis Bujanda: He declares no conflicts of interest.
Dr Rosiered Brownson-Smith: “no CoI’s to declare”