The relative and attributable risks of cardia and non-cardia gastric cancer associated with Helicobacter pylori infection in China: a case-cohort study

摘要

BackgroundHelicobacter pyloriinfection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-basedH pyloriscreening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations ofH pyloriinfection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults.MethodsA case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30–79 years from ten areas in China (Qingdao, Haikou, Harbin, Suzhou, Liuzhou, Henan, Sichuan, Hunan, Gansu, and Zhejiang), and included 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants who were cancer-free and alive within the first two years since enrolment in 2004–08.H pyloribiomarkers were measured in stored baseline plasma samples using a sensitive immunoblot assay (HelicoBlot 2.1), with adapted criteria to defineH pyloriseropositivity. Cox regression was used to estimate adjusted hazard ratios (HRs) for NCGC and CGC associated withH pyloriinfection. These values were used to estimate the number of gastric cancer cases attributable toH pyloriinfection in China.FindingsOf the 512?715 adults enrolled in the China Kadoorie Biobank between June, 2004, and July, 2008, 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants were selected for analysis. The seroprevalence ofH pyloriwas 94·4% (95% CI 92·4–96·4) in NGCG, 92·2% (89·7–94·7) in CGC, and 75·6% (71·8–79·4) in subcohort participants.H pyloriinfection was associated with adjusted HRs of 5·94 (95% CI 3·25–10·86) for NCGC and 3·06 (1·54–6·10) for CGC. Among the seven individual infection biomarkers, cytotoxin-associated antigen had the highest HRs for both NCGC (HR 4·41, 95% CI 2·60–7·50) and CGC (2·94, 1·53–5·68). In this population, 78·5% of NCGC and 62·1% of CGC cases could be attributable toH pyloriinfection.H pyloriinfection accounted for an estimated 339?955 cases of gastric cancer in China in 2018.InterpretationAmong Chinese adults,H pyloriinfection is common and is the cause of large numbers of gastric cancer cases. Population-based mass screening and the eradication ofH pylorishould be considered to reduce the burden of gastric cancer in high-risk settings.FundingCancer Research UK, Wellcome Trust, UK Medical Research Council, British Heart Foundation, Kadoorie Charitable Foundation, National Key Research and Development Program of China, and National Natural Science Foundation of China.