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Genetic susceptibility, environmental risk factors, and incident gastric cancer risk among individuals with different Helicobacter pylori infection status: a population-based study

Hengmin Xu, Hui Ma, Yuxin Wang, Xinling Wang, Xuan Han, Wenjing Zhao, Yang Zhang, Tong Zhou, Jingying Zhang, Weicheng You, Wenqing Li and Kaifeng Pan
Cancer Biology & Medicine July 2026, 20260145; DOI: https://doi.org/10.20892/j.issn.2095-3941.2026.0145

Article Figures & Data

Figures

  • (A) Procedure of inclusion and exclusion of study populations. (B) H. pylori-stratified associations of 14 genetic variants showing nominal heterogeneity in gastric cancer risk. (C) Hazard ratios for gastric cancer across polygenic risk score quintiles by H. pylori infection status. (D) Cumulative incidence of gastric cancer across polygenic risk score groups by H. pylori status. (E) Associations of H. pylori eradication and environmental risk score with gastric cancer risk by genetic risk group. CI, confidence interval; ERS, environmental risk score; GC, gastric cancer; FDR, false discovery rate; H. pylori, Helicobacter pylori; HR, hazard ratio; UBT, urea breath test.
    (A) Procedure of inclusion and exclusion of study populations. (B) H. pylori-stratified associations of 14 genetic variants showing nominal heterogeneity in gastric cancer risk. (C) Hazard ratios for gastric cancer across polygenic risk score quintiles by H. pylori infection status. (D) Cumulative incidence of gastric cancer across polygenic risk score groups by H. pylori status. (E) Associations of H. pylori eradication and environmental risk score with gastric cancer risk by genetic risk group. CI, confidence interval; ERS, environmental risk score; GC, gastric cancer; FDR, false discovery rate; H. pylori, Helicobacter pylori; HR, hazard ratio; UBT, urea breath test.
    Figure 1

    (A) Procedure of inclusion and exclusion of study populations. (B) H. pylori-stratified associations of 14 genetic variants showing nominal heterogeneity in gastric cancer risk. (C) Hazard ratios for gastric cancer across polygenic risk score quintiles by H. pylori infection status. (D) Cumulative incidence of gastric cancer across polygenic risk score groups by H. pylori status. (E) Associations of H. pylori eradication and environmental risk score with gastric cancer risk by genetic risk group. CI, confidence interval; ERS, environmental risk score; GC, gastric cancer; FDR, false discovery rate; H. pylori, Helicobacter pylori; HR, hazard ratio; UBT, urea breath test.

Tables

  • Table 1

    Associations of environmental risk score and its joint effects with genetic risk on gastric cancer

    No. of cases (person-years)HR (95% CI)aP
    Environmental risk scoreb
    Per SD increase621 (17,329)1.13 (1.04–1.22)0.0023
     Low ERS482 (13,840)Ref
     High ERS139 (3,489)1.29 (1.06–1.55)0.0092
    Grouped by genetic risk
     Low genetic risk
      Low ERS74 (2,932)Ref
      High ERS15 (671)0.79 (0.45–1.38)0.41
     Medium genetic risk
      Low ERS297 (8,113)1.68 (1.30–2.18)8.39 × 10−5
      High ERS90 (2,206)2.20 (1.60–3.01)8.86 × 10−7
     High genetic risk
      Low ERS111 (2,795)2.04 (1.51–2.76)3.37 × 10−6
      High ERS34 (612)4.63 (3.07–6.98)2.90 × 10−13
      P-intc0.042

    • ↵aHRs were estimated using Cox proportional hazards models adjusted for age and gender, and 10 principal components (for joint analyses only).

    • ↵bThe environmental risk score (ERS) was constructed based on 10 environmental lifestyle and dietary risk factors. Individuals in the top 20% of the distribution were classified as having high ERS, while the remainder were defined as low ERS.

    • ↵cP-interaction value (P-int) of genetic risk group and ERS was calculated using the likelihood ratio tests comparing models with and without the interaction term.

    • CI, confidence interval; HR, hazard ratio.

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