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H. Pylori

Chronic infections with different pathogens are responsible for 13% of total cancer globally (an estimated 2.2 million new cancer cases annually), with more than a third in China.

Gastric cancer is the second leading cause of cancer death globally, with particularly high rates in China. Although previous studies have demonstrated a clear causal link between H. pylori infection and non-cardia gastric cancer (NCGC), the estimated relative risks vary considerably between different studies. There is also conflicting evidence about the role of H. pylori in the aetiology of cardia gastric cancer (CGC), which occurs at the top of the stomach, and accounts for 30% of total gastric cancer globally.

Using a highly-sensitive assay to detect H. pylori infection of the stored blood samples in a large, carefully designed nested case-cohort study, CKB has provided robust new evidence about the role of H. pylori infection in aetiology of both CGC and NCGC.

Overall among the 500 sub-cohort CKB participants 75.6% tested positive for H. pylori infection. Individuals who tested positive with H. pylori  were six times more likely than those who were H. pylori  negative to develop NCGC and three times more likely to develop CGC. These risk estimates were twice as strong as those reported in previous Chinese studies which used less sensitive assays. We estimated that H. pylori accounted for approximately 340,000 new gastric cancers each year in China, including about 80% of the NCGC and 60% of the CGC cases (Lancet Public Health 2021).

These updated risk estimates should help refine global disease burden estimation and inform the development of mass H. pylori screening and eradication programmes for primary prevention of gastric cancer in high risk populations.

Chronic infections with other pathogens such as hepatitis virus, human papillomavirus (HPV), and fluke worms also play an important roles in cancer development and progression.

To overcome the limitations of previous studies that tended to focus on a single pathogen with a single cancer, we have developed, in close collaboration with German Cancer Research Center (DKFZ) and UK Biobank, a custom-designed multiplex serological panel that can measure more than 45 antigens from approximately 20 pathogens simultaneously. Our pilot study involving 2000 randomly selected participants confirmed high prevalence of most infections, and demonstrated significant regional, gender and intergenerational variations of sero-prevalence for certain pathogens in Chinese adults. Co-infection with multiple pathogens was common: 25% of participants were sero-positive for more than 10 pathogens.

Our large CRUK-funded research programme will comprehensively assess the roles of chronic infections with multiple pathogens in aetiology of multiple cancers.

Impact of research

CKB’s updated risk estimates should help refine global disease burden estimation and inform infection-related cancer prevention and control policy making, which will be of benefit to people in low-middle income countries and across the world.