Helicobacter pylori multiplex serology and risk of non-cardia and cardia gastric cancer: a case-cohort study and meta-analysis

Pang Yao; Christiana Kartsonaki; Julia Butt; Rima Jeske; Catherine de Martel; Martyn Plummer; Yu Guo; Sarah Clark; Robin G Walters; Yiping Chen; Daniel Avery; Jun Lv; Canqing Yu; Hao Wang; Michael Hill; Richard Peto; Liming Li; Tim Waterboer; Zhengming Chen; Iona Y Millwood; Ling Yang

doi:10.1093/ije/dyad007

Helicobacter pylori multiplex serology and risk of non-cardia and cardia gastric cancer: a case-cohort study and meta-analysis

Int J Epidemiol. 2023 Aug 2;52(4):1197-1208. doi: 10.1093/ije/dyad007.

Authors

Pang Yao¹, Christiana Kartsonaki^{1

2}, Julia Butt³, Rima Jeske³, Catherine de Martel⁴, Martyn Plummer⁵, Yu Guo⁶, Sarah Clark^{1

2}, Robin G Walters^{1

2}, Yiping Chen^{1

2}, Daniel Avery¹, Jun Lv^{7

8}, Canqing Yu^{7

8}, Hao Wang⁹, Michael Hill^{1

2}, Richard Peto¹, Liming Li^{7

8}, Tim Waterboer³, Zhengming Chen^{1

2}, Iona Y Millwood^{1

2}, Ling Yang^{1

2}

Affiliations

¹ Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
² Medical Research Council Population Health Research Unit (MRC PHRU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
³ Infections and Cancer Epidemiology Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁴ Early Detection, Prevention and Infections Branch, International Agency for Research on Cancer, Lyon, France.
⁵ Department of Statistics, University of Warwick, Coventry, UK.
⁶ National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
⁸ Center for Public Health and Epidemic Preparedness & Response, Peking University, Beijing, China.
⁹ NCDs Prevention and Control Department, Zhejiang CDC, Zhejiang, China.

Abstract

Background: Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but uncertainty remains about the associations between sero-positivity to different H. pylori antigens and risk of NCGC and cardia gastric cancer (CGC) in different populations.

Methods: A case-cohort study in China included ∼500 each of incident NCGC and CGC cases and ∼2000 subcohort participants. Sero-positivity to 12 H. pylori antigens was measured in baseline plasma samples using a multiplex assay. Hazard ratios (HRs) of NCGC and CGC for each marker were estimated using Cox regression. These were further meta-analysed with studies using same assay.

Results: In the subcohort, sero-positivity for 12 H. pylori antigens varied from 11.4% (HpaA) to 70.8% (CagA). Overall, 10 antigens showed significant associations with risk of NCGC (adjusted HRs: 1.33 to 4.15), and four antigens with CGC (HRs: 1.50 to 2.34). After simultaneous adjustment for other antigens, positive associations remained significant for NCGC (CagA, HP1564, HP0305) and CGC (CagA, HP1564, HyuA). Compared with CagA sero-positive only individuals, those who were positive for all three antigens had an adjusted HR of 5.59 (95% CI 4.68-6.66) for NCGC and 2.17 (95% CI 1.54-3.05) for CGC. In the meta-analysis of NCGC, the pooled relative risk for CagA was 2.96 (95% CI 2.58-3.41) [Europeans: 5.32 (95% CI 4.05-6.99); Asians: 2.41 (95% CI 2.05-2.83); Pheterogeneity<0.0001]. Similar pronounced population differences were also evident for GroEL, HP1564, HcpC and HP0305. In meta-analyses of CGC, two antigens (CagA, HP1564) were significantly associated with a higher risk in Asians but not Europeans.

Conclusions: Sero-positivity to several H. pylori antigens was significantly associated with an increased risk of NCGC and CGC, with varying effects between Asian and European populations.

Keywords: H. pylori antigens; Helicobacter pylori; CagA; cardia gastric cancer (CGC); non-cardia gastric cancer (NCGC); regional difference.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Bacterial
Cohort Studies
Helicobacter Infections* / complications
Helicobacter Infections* / epidemiology
Helicobacter pylori*
Humans
Risk Factors
Stomach Neoplasms* / epidemiology

Substances

Antigens, Bacterial

Abstract

Publication types

MeSH terms

Substances

Grants and funding