Individuals with high genetic risk for gastric cancer may benefit from H. pylori treatment



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Key takeaways:

  • A polygenic risk score of 12 genomic loci was associated with risk for gastric cancer (HR = 2.54).
  • The odds of gastric cancer increased 1.83-fold for the highest vs. lowest polygenic risk score decile.

Treatment for Helicobacter pylori infection was associated with reduced risk for gastric cancer among patients with a high genetic risk, suggesting that chemoprevention should be personalized to genetic risk, according to data.

“A heritability of 22% has been previously estimated for gastric cancer,” Heng-Min Xu, BS, of Peking University Cancer Hospital and Institute, and colleagues wrote in JAMA Network Open. “Genome-wide association studies (GWASs) of a case-control design have identified multiple genomic loci with predisposition to gastric cancer, while a prospective study further suggested increased risk of incident gastric cancer associated with a high polygenic risk score (PRS).”



H. pylori treatment associated with a reduced risk for gastric cancer among those with high genetic risk.

Data derived from: Xu H, et al. JAMA Netw Open. 2024;doi:10.1001/jamanetworkopen.2024.13708.

Using follow-up data from the Shandong Intervention Trial (SIT) and China Kadoorie Biobank (CKB), Xu and colleagues investigated genetic variants associated with progression of gastric lesions and risk for incident gastric cancer, as well as the effect of H. pylori treatment and nutritional supplementation among individuals at high and low genetic risk.

Researchers first conducted a longitudinal GWAS to identify genetic variants among 2,816 participants (mean age, 46.95 years; 50.75% women) in the SIT cohort and 100,228 participants (mean age, 53.69 years; 57.23% women) in the CKB cohort. A cohort of 1,394 participants (mean age 54.54 years, 37.8% women), including 702 with gastric cancer and 692 controls, was used for external validation of PRS associated with gastric cancer risk.

During a follow-up period of 27.1 years, researchers identified 147 and 825 cases of gastric cancer in the SIT and CKB cohorts, respectively.

According to results, a PRS of 12 independent signals of genomic loci was associated with risk for gastric cancer in the CKB cohort (highest vs. lowest decile of PRS: HR = 2.54; 95% CI, 1.8-3.57). Researchers further reported a significant association between the PRS and gastric cancer risk in the validation cohort, in which the odds of gastric cancer increased 1.83-fold (95% CI, 1.11-3.05) for the highest vs. lowest PRS decile.

Further, results showed H. pylori treatment was associated with reduced risk for gastric cancer among those with high genetic risk, defined as top 25% of PRS (HR = 0.45; 95% CI, 0.25-0.82), but not among those with a low genetic risk (HR = 0.81; 95% CI, 0.5-1.34).

“This cohort study found that appropriate primary gastric cancer prevention may be associated with lower risk of gastric cancer among those with high genetic risk, suggesting that chemoprevention strategies should be tailored to genetic risk for effective gastric cancer prevention,” Xu and colleagues wrote. “Integrating host and genetic characteristics for fine risk stratification and, ideally, with tailored regimen selection, would be warranted in future endeavors for optimized primary prevention of gastric cancer.”

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