幽门螺杆菌治疗和营养补充可以预防胃癌 (GC)，但这些有益效果是否仅适用于潜在的遗传亚群以及这些化学预防策略是否可以抵消高遗传风险仍然未知。胃病变和GC风险，并根据遗传风险水平评估幽门螺杆菌治疗和营养补充的益处。本队列研究使用了山东干预试验（SIT，1989-2022）和中国嘉道理生物库（CKB， 2004-2018）在中国。在 SIT 的基础上，进行了一项纵向全基因组关联研究，以确定胃病变进展的遗传变异。在一组随机抽样的 CKB 参与者（第 1 组）中检查了 GC 事件的显着变异。结合独立变异的多基因风险评分（PRS）在剩余 CKB 参与者（第 2 组）和 Linqu.H pylori 治疗和营养补充的独立病例对照研究中评估了 GC 风险。主要结果是胃病变的进展（仅 SIT）和 GC 风险。在具有不同遗传风险水平的 SIT 参与者中评估了幽门螺杆菌治疗和营养补充与 GC 的关联。我们的分析包括 2816 名 SIT 参与者（平均 [SD] 年龄，46.95 [9.12] 岁；1429 名 [50.75%] 女性） CKB 中的 100228 名参与者（平均 [SD] 年龄，53.69 [11.00] 岁；女性 57357 名 [57.23%]），在随访期间发现 SIT 中 147 例 GC 病例，CKB 中 825 例 GC 病例。得出了整合与胃部病变进展和发生 GC 风险相关的 12 个基因组位点的 PRS，该 PRS 与 CKB 中的 GC 风险相关（PRS 的最高与最低十分位数：风险比 [HR]，2.54；95% CI，1.80-3.57）并在 702 名病例参与者和 692 名对照参与者的分析中得到进一步验证（平均 [SD] 年龄，54.54 [7.66] 岁；527 名女性 [37.80%]；比值比，1.83；95% CI，1.11-3.05）。幽门螺杆菌治疗仅与高遗传风险个体（PRS 前 25%：HR，0.45；95% CI，0.25-0.82）的 GC 风险降低相关，但与低遗传风险个体（HR，0.81；95%）无关。 CI，0.50-1.34；P 表示相互作用 = .03）。维生素（相互作用 P = .93）或大蒜（相互作用 P = .41）补充剂没有发现这种效果改变。这项队列研究的结果表明，幽门螺杆菌治疗可以抵消 GC 的高遗传风险，建议一级预防可以根据遗传风险进行调整，以实现更有效的预防。

Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown.To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk.This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu.H pylori treatment and nutrition supplementation.Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk.Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation.The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.