Burden and Correlates of Multiple Chronic Infections and Their Associations With Cancer Incidence in Chinese Adults: A Large Case‐Cohort Study

Several oncogenic pathogens cause specific cancers, but uncertainties remain about many other chronic infections, combined pathogen effects and evidence from non-European populations. We conducted a case-cohort study of ~30,000 site-specific incident cancer cases and > 8000 subcohort participants nested within the China Kadoorie Biobank. Baseline plasma was assayed for IgG antibodies against 47 antigens from 20 pathogens (16 viruses, 3 bacteria, 1 parasite) using an Automated Multiplex Serology assay. We described seroprevalence by age, sex, areas and lifestyle factors; estimated adjusted odd ratios for correlates of pathogen seropositivity in the subcohort using multivariable logistic regression and adjusted hazard ratios for overall and selected cancers using Prentice-weighted Cox models. Among subcohort participants, seroprevalence for most pathogens varied and was significantly associated with sex, region and birth cohort. Participants were seropositive for a mean of ~10 pathogens. Compared with seronegative participants, those seropositive for seven pathogens had significantly higher overall cancer risk, particularly for HCV (HR = 2.18, 95% CI: 1.90-2.49), CMV (1.23, 1.08-1.40) and HSV-2 (1.14, 1.09-1.18) and HPV-16 oncogenes (e.g., E6: 1.57, 1.40-1.75). Lower risks were observed for HSV-1 (0.88, 0.81-0.95) and among those with fewer co-infections. There were expected positive associations of liver cancer with HBV (2.29, 2.06-2.54) and HCV (7.05, 4.31-11.54) and of stomach cancer with H. pylori (1.91, 1.68-2.17). In Chinese adults, multiple chronic infections were associated with risk of overall and certain selected cancers. Further research is warranted to investigate pathogen-specific and co-infection-related risks of site-specific cancers.