Spotlight on H. pylori and gastric cancer risk
Recent studies in Japan found that eradication of Helicobacter pylori infection may be particularly important for gastric cancer prevention in certain patients and that lack of follow-up after eradication is a risk factor for undifferentiated gastric cancer.
Two studies published in the past month provided more insight on Helicobacter pylori infection as a risk factor for gastric cancer.
The first study found that DNA damage induced by H. pylori, if not correctly repaired, may be a major driver of gastric carcinogenesis. Researchers looked at the association between germline pathogenic variants in 27 cancer-predisposing genes and the risk of gastric cancer in 10,426 patients with gastric cancer and 38,153 controls from BioBank Japan. They also assessed the combined effect of pathogenic variants and H. pylori infection status on gastric cancer risk and calculated the cumulative risk in 1,433 patients with gastric cancer and 5,997 controls from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Results were published March 30 by the New England Journal of Medicine.
Inherited pathogenic variants in nine genes were associated with gastric cancer risk: APC, ATM, BRCA1, BRCA2, CDH1, MLH1, MSH2, MSH6, and PALB2. There was a much larger interaction between variants in four of the nine gastric cancer risk genes that are involved in the DNA-repair pathway of homologous recombination (ATM, BRCA1, BRCA2, and PALB2) compared with that of interactions between these variants and other environmental factors (smoking, drinking, obesity, and sodium intake), and the interaction was independent of the other environmental factors. The cumulative risk of gastric cancer at age 85 years (i.e., lifetime risk) was less than 5% in those without H. pylori infection, regardless of carrier status. In contrast, the lifetime risk was higher among those with H. pylori infection who were carriers of pathogenic variants in homologous-recombination genes versus noncarriers (45.5% [95% CI, 20.7% to 62.6%] vs. 14.4% [95% CI, 12.2% to 16.6%]). Limitations of the study include its retrospective design and the fact that there are biologic differences between the East Asian and Western types of H. pylori, which may limit generalization, the authors noted. “These findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed and suggests that DNA damage induced by H. pylori, if repaired incorrectly or not at all, is a major driver of gastric carcinogenesis,” an accompanying editorial noted.
The second study found that lack of follow-up after H. pylori eradication is a significant risk factor for undifferentiated gastric cancer. Researchers analyzed gastric cancer lesions from patients who had successfully completed H. pylori eradication and who had had upper GI endoscopy between January 2004 and March 2016 at a hospital in Japan. They categorized gastric cancer tumors as differentiated or undifferentiated histologic types (the latter of which has not been evaluated in detail in the literature because of its low incidence) and compared the clinicopathological features between groups to determine risk factors of undifferentiated gastric cancer. Results were published March 31 by PLOS One.
The study evaluated 129 tumors from 115 patients, 113 in the differentiated group and 16 in the undifferentiated group. Depressed-type tumors (P=0.024) and sub-submucosal invasion (P<0.001) were significantly higher in the undifferentiated group, which also had larger tumor diameters than the differentiated group (25.9±7.3 mm vs. 13.2±10.2 mm; P<0.001). Female sex (odds ratio [OR], 3.24 [95% CI, 1.02 to 10.37]; P=0.047) and absent follow-up (OR, 4.99 [95% CI, 1.60 to 15.57]; P=0.006) were significant independent risk factors for undifferentiated gastric cancer. The study was limited by the small sample size of patients with undifferentiated gastric cancer; however, the 16 cases make up the largest number in studies that have examined risk factors for this condition, the authors noted. The results suggest that diligent long-term follow-up after H. pylori eradication is necessary, as early endoscopic detection of gastric cancer may reduce conversion to undifferentiated gastric cancer and subsequent tumor progression, they noted.