Reducing chronic infections from the bacterium Helicobacter pylori would be a key strategy for preventing stomach cancer, according to research published today in The Lancet Public Health.
Gastric (stomach) cancer is the second leading cause of cancer death globally, responsible for around 770,000 deaths in 2020, with China accounting for over half (478,000) of the global disease burden. One of the most important and preventable causes of gastric cancer is infection by the bacterium Helicobacter pylori (H. pylori), which attacks the stomach lining. Based on evidence mainly from Western populations, the World Health Organization estimated that H. pylori was responsible for 0.8 million new cases of gastric cancer globally in 2018.
Previous studies have demonstrated a clear link between H. pylori infection and non-cardia gastric cancer (NCGC): cancer in the main area of the stomach. However, the estimated risk from infection varies considerably across these studies, depending on the study design and type of assay used. Moreover, there was conflicting evidence on whether H. pylori also causes cardia gastric cancer (CGC), which occurs at the top of the stomach where it joins the oesophagus. CGC accounts for about a third of gastric cancer cases globally.
To generate conclusive evidence, Oxford Population Health researchers used high-quality data from the prospective China Kadoorie Biobank (CKB) study.
The CKB study recruited over half a million adults from ten diverse geographical regions across China between 2004 and 2008. The study participants completed a baseline survey, then their health outcomes were tracked through electronic linkage to death and cancer registries, and national health insurance databases. H. pylori infection was determined using a highly-sensitive immunoblot assay on the stored blood samples taken during the baseline survey. The assay tests for the presence of seven diagnostic antibodies which bind to H. pylori proteins. This is the first time that immunoblot assays have been used on a large scale to assess H. pylori infection in China.
After an average follow-up period of ten years:
- There were 3,464 reported cases of gastric cancer, including 2,035 cases of NCGC and 437 cases of CGC. The incidence rate was nearly three times higher in men than in women.
- Compared with H. pylori negative study participants, those who had been infected by the bacterium were six times more likely to develop NCGC and three times more likely to develop CGC.
- Adjusting the data to take into account other risk factors (such as smoking, alcohol and family history of cancer) did not significantly alter these risk estimates.
- The proportion of gastric cancer cases caused by H. pylori was estimated to be 78.5% for NCGC and 62.1% for CGC.
- Based on the 2018 China cancer statistics, H. pylori infection would be responsible for ~340,000 new cases of gastric cancer (271,000 NCGC, 69,000 CGC) in China each year.
Dr Ling Yang, senior epidemiologist in Oxford Population Health, who led the investigation said: ‘Our study showed that H. pylori infection was associated with a six-fold higher risk of NCGC and a three-fold higher risk of CGC. These relative risk estimates were twice as strong as those estimated in Chinese adults by previous studies that used less sensitive assays.’
Professor Zhengming Chen, principal investigator in the UK for the China Kadoorie Biobank and a senior author of the paper said: ‘These updated estimates of the risk and burden of gastric cancer due to H. pylori infection will help refine global disease burden estimates and help policy makers develop and implement suitable strategies for cancer prevention locally and globally. Population-level H. pylori mass screening and eradication should be considered as a key strategy for gastric cancer prevention in China and high-risk settings globally.’
The work was mainly funded by Cancer Research UK and also involved collaborators from China and the International Agency for Research on Cancer. Last year Cancer Research UK also awarded a five-year programme grant to CKB to comprehensively investigate the roles of 19 different pathogens in cancer.