Authors
Zong-Chao Liu, Yu-Xin Wang, Heng-Min Xu, Xuan Han, Wen-Jing Zhao, Hui Ma, Yang Zhang, Jing-Ying Zhang, Tong Zhou, Wei-Cheng You, Kai-Feng Pan, Wen-Qing Li
Published in
Innovation (Cambridge (Mass.)). Volume 7. Issue 10. Pages 101402. Oct 05, 2026. Epub Apr 16, 2026.
Abstract
Population-based Helicobacter pylori screen-and-treat is a priority for gastric cancer (GC) prevention, yet the preventive effect varies across individuals, and the determinants of this heterogeneity remain insufficiently understood. As large-scale prevention efforts expand globally, identifying individuals most likely to benefit is increasingly important. We analyzed two randomized trials, the Mass Intervention Trial in Linqu, Shandong Province (MITS; ChiCTR-TRC-10000979; n = 1,740), and the Shandong Intervention Trial (SIT; NCT00339768; n = 1,811), to characterize genetically determined heterogeneous treatment effects of H. pylori eradication for GC prevention. We identified 11 genetic variants that modified the preventive efficacy of eradication and integrated their genotype-specific conditional average treatment effects into a polygenic treatment benefit score (PTBS). We further compared a benefit-based strategy prioritizing individuals predicted to derive greater benefit for GC prevention with a risk-based strategy defined by a polygenic risk score and assessed whether benefit-based subgroups exhibited differential residual GC risk post-eradication. With the PTBS, targeting the high-treatment-benefit individuals conferred stronger protection against GC (MITS, hazard ratio [HR] = 0.44, 95% confidence interval [CI] 0.35-0.54, number needed to treat [NNT] = 56; SIT, HR = 0.20, 95% CI 0.10-0.41, NNT = 26) than treating all H. pylori-positive participants or those of high genetic risk. PTBS further stratified residual GC risk among individuals post-treatment (MITS, HR = 0.65, 95% CI 0.52-0.81; SIT, HR = 0.27, 95% CI 0.13-0.56, for high-treatment-benefit individuals) and was associated with slower precancerous lesion progression. Our findings suggest that host genetic factors modulate the preventive efficacy of H. pylori eradication and that incorporating genotype-specific heterogeneous treatment effects provides a framework for enhancing the precision of population-based screen-and-treat programs while supporting post-eradication risk management.
PMID:
42891186
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.
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