Helicobacter Pylori: Relationship to Cancer and Dubious Beneficial Claims

I found a recent review (Gastroenterol 2015; 148: 719-31) regarding Helicobacter pylori (HP) of interest.  David Graham explores the issue of HP eradication with regard to cancer and whether there are benefits to the infection that result in detrimental effects with HP eradication.

The potential mechanisms in which HP infection can increase the risk of gastric cancer are depicted in Figure 2; the most important:

  • Inflammation induced by infection
  • Genetic/epigenetic changes –> genetic instability in gastric epithelial cells

Lessons regarding eradication therapy:

  • Sequential therapy has been shown in some studies to be effective/superior (in Italy) yet inferior in others (eg. Korea).  “The results are explained entirely by differences in patterns of drug resistance, which typically were not assessed before studies were initiated.”
  • Findings from many studies cannot be applied to other populations without resistance data.

Does HP infection reduce the risk of obesity or childhood asthma?  Probably not.

  • “Any claim that a major human pathogen also might provide a meaningful health benefit, and that plans to eradicate it should be reconsidered, is guaranteed to elicit interest from the press.”
  • As a counter example, Dr. Graham notes “because 2 events are associated does not mean that one causes the other. For example, one study reported a correlation between the number of storks in Brandenburg, Germany, and the birth rate in Berlin.” [Backen MB. Harm. In: Bracken MB. Risk, chance, and causation. New Haven: Yale University Press, 2013; 108-09.]
  • He notes that HP can both promote or inhibit acid secretion/acid reflux.  Increased acid secretion with resultant esophageal disease could increase the risk of adenocarcinoma of the esophagus; however, “the risk of developing adenocarcinoma of the stomach remains higher than the risk of adenocarcinoma of the esophagus.”  This indicates that if there is an increased esophageal cancer risk, eradication would still be favorable by lowering gastric cancer risk.
  • Asthma: “overall, the studies do not support the hypotheses that increases in childhood asthma were related to the absence of H pylori.”
  • Obesity: “A meaningful causative association between H pylori and obesity is unlikely.”
Screen Shot

Screen Shot

Take-home message: H pylori is a pathogen and should be treated as such.

Related blog posts:

University of Chicago

University of Chicago

Preventing Cancer in patients with Barrett’s Esophagus

Though Barrett’s esophagus is rare in pediatric gastroenterology, concerns about esophageal cancer are fairly frequent.  In addition, some conditions that increase the risk of esophageal adenocarcinoma start in childhood.

One way to lessen the risk of Barrett’s esophagus in adults is through the use of medications (Gastroenterology 2012; 142: 442-52).  This study was a pooled analysis of six population-based trials with a total of 1226 esophageal adenocarcinoma (EAC) patients and 1140 esophagogastric junctional adenocarcinoma (EGJA) patients.  NSAIDs (aspirin and nonaspirin) lowered the risk of both EAC and EGJA, with OR of 0.68 and 0.83 respectively.

Although this study suggests a possible role for NSAIDs in preventing cancer in patients with Barrett’s esophagus, the risks and benefits for this intervention need to be individualized.

Related previous blog post: More bad news for smokers

Additional references:

  • -Gastroenterology 2011; 141: 2000. Lower risk of Barrett’s in pts taking NSAIDs & statins. n=570.
  • -Gastroenterology 2011; 141: 1179. Overall, patients with BE and LGD have a low annual incidence of EAC, similar to nondysplastic BE. There are no risk factors for progression and there is significant interobserver variation in diagnosis, even among expert pathologists.
  • -NEJM 2011; 365: 1375. Large Danish study, n=11028. Lower incidence of Barrett’s than previous estimates. Relative risk of 11.3 compared to general population for adenoca of Esophagus with absolute annual risk of 0.12%. Barrett’s patients have the same life expectancy as general population (ed. pg 1437). Detecting cancer only ~1 in 1460 scopes with screening whereas Barrett’s detected in 10% of pts.
  • -Gastroenterology 2011; 141: 417, 460. Durable effects of ablation, n=127..
  • -Gastroenterology 2011; 140: 1084. AGA statement on Barrett’s . Recs screening only in those with multiple risk factors (age 50, male, chronic GERD, white, incr BMI)
  • -Clin Gastro & Hep 2010; 8: 565. Guidelines suggest that screening for Barrett’s is not justified w/o alarm symptoms (dysphagia, odynophagia, wt loss, anemia, hematemesis)
  • -Gastroenterology 2010; 138: 2260. n=11,823. Decrease risk of esophageal adenoCa in patients taking NSAIDs & statins.
  • -Gastroenterology 2010; 138: 854. Nice review.
  • -Gastroenterology 2010; 138: 5. Survival equivalent to general population according to Mayo study, n=366. In Barrett’s patients, leading cause of death was cardiovascular (28%). Esophageal cancer resulted in 7% of deaths. Study presented at ACG Oct 26, 2009.
  • -Clin Gastro & Hepatology 2009; 7: 1266. no benefit from surgery for Barrett’s & unclear if chemoprevention works.
  • -Gastroenterology 2009; 137: 763. Suggests surveillance with Barrett’s is not beneficial.
  • -NEJM 2009; 360: 2277, 2353.. Radiofrequency ablation can be effective.
  • -Gut 2008; 57: 1200-06. Utility of endoscopic Rx.
  • -Clin Gastro & Hep 2008; 6: 1206; editorials: 1180, 1181, 1183.. n=2107 with Barrett’s. 79 w surgery and 80 w endoscopic Rx.
  • -Gastro & Hep 2006; 2: 468. 2-8% of pts in general population have Barrett’s. >90% of ptsc Barretts will never develop cancer. Screening has not been proven to be effective in lowering rate of death from cancer. ~40% of US population has heartburn; only 8000-9000/yr develop esoph adenoCa. Also, the presence of Barrett esophagus does not decrease life expectancy.
  • -Gastroenterology 2005; 129: 1825-31. 1.6% incidence of BE in adult Swedish population. Alcohol, smoking increase risk.