| Title: | Gastric cancer risk associated with autoimmune gastritis-predisposing HLA alleles: a national prospective cohort study |
| Journal: | International Journal of Surgery |
| Published: | 6 May 2026 |
| DOI: | https://doi.org/10.1097/js9.0000000000005326 |
Publication 20160
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Background: The link between autoimmune gastritis (AIG) and gastric cancer (GC) remains debated, hampered by diagnostic challenges and confounding factors like Helicobacter pylori . AIG-predisposing Human leukocyte antigen (HLA) alleles offer a genetic proxy to investigate this relationship. Methods: 439 828 UK Biobank participants with HLA genotypes were enrolled. Exposure was defined as carriage of established AIG-associated HLA alleles. The primary outcome was incident GC. Cox proportional hazards models assessed associations, adjusting for demographics, lifestyle, ancestry, H. pylori , and precancerous lesions. Multiplicative interactions between alleles and comorbid conditions were tested. Results: Over a median of 13.27 years follow-up, 904 incident GC cases occurred. In the fully adjusted model, HLA-DRB1*04:07 (HR: 1.55, 95% CI: 1.04-2.31), DRB1*04:10 (14.13, 1.95-102.32), and DQB1*03:04 (2.79, 1.25-6.23) were nominally associated with elevated GC risk. Notably, HLA-DQB1*03:04 remained significant after FDR correction. Compared with individuals without polyps or benign neoplasms, the association between DQB1*03:04 and GC was more pronounced among those with polyps (HR = 16.57) and benign neoplasms (HR = 25.72). Conclusion: Specific AIG-predisposing HLA alleles were identified as risk factors for GC, independent of H. pylori . The interaction between DQB1*03:04 and precancerous lesions suggests high-risk subgroups warranting intensified surveillance. HLA genotyping may help identify individuals at elevated GC risk, particularly among those with polyps or benign neoplasms. </p>
8 Authors
- Shengan Zhang
- Liang Dai
- Linfeng Meng
- Ziqi Zhang
- Wei Qian
- Li Zhang
- Wei Huang
- Guang Ji
1 Application
| Application ID | Title |
|---|---|
| 221713 | Exploring the associations of lifestyle, environmental and genetic factors on metabolic diseases and cancer |
Enabling scientific discoveries that improve human health