Background: Pancreatic cancer has a very poor prognosis, partly because it is usually diagnosed late. Some risk factors exist, but these only explain a small proportion of the risk of developing pancreatic cancer. Several studies have explored the association between infections and risk of pancreatic cancer, many of which focus on Helicobacter pylori (H. pylori) and hepatitis viruses, but with no clear evidence on their relations.
Objectives: To assess the associations between seropositivity for 20 pathogens measured using 40 antigens with risk of developing pancreatic cancer in the future.
Methods: We conducted a case-cohort study on cancer in the China Kadoorie Biobank, a prospective cohort study of about half a million Chinese adults recruited in 2004-08. The study included 993 cases of pancreatic cancer which accrued over about 10 years of follow-up through linkage with cancer registries, death registries, and health insurance records, and a subcohort of 8210 individuals selected randomly from the cohort at baseline. IgG antibody titres against antigens covering a range of pathogens including viruses, bacteria, and parasites were measured in stored plasma samples obtained from participants at study entry. The associations of seropositivity for each pathogen with risk of pancreatic cancer were assessed using Cox regression with Prentice weighting, adjusting for age, sex, and region, with time in study as the time scale.  The UK Biobank, a prospective cohort study of about half a million adults from the United Kingdom, contains multiplex serology data on 9689 individuals, including 38 pancreatic cancer cases. The associations of seropositivity for each pathogen with risk of pancreatic cancer were assessed using Cox regression, adjusting for age, sex, and assessment centre, with time in study as the time scale.
Results: In the subcohort of the China Kadoorie Biobank seroprelalence of pathogens varied widely, with HCV having less than 1% and EBV over 99.5%. Cytomegalovirus (CMV), a herpes virus with seroprevalence 99% in the subcohort had some evidence of an association with risk of pancreatic cancer (HR 3.30, 95% CI 1.01-10.82). There was no evidence of an association of H. pylori seropositivity (HR 1.03, 95% CI 0.88-1.20), Hepatitis B virus (HR 1.01, 95% CI 0.87-1.17), or other of the pathogens included with risk of pancreatic cancer. In the UK Biobank the association of CMV with pancreatic cancer was consistent, with a HR of 1.90 (95% CI 0.89-4.05).
Conclusions: Infection with CMV may be associated with future risk of pancreatic cancer. It is unlikely that H. pylori has an important role in pancreatic cancer development. CMV has been implicated in various types of cancer, including pancreatic cancer and has been used in the development of certain treatments. The role of CMV in the development and progression of pancreatic cancer warrants further investigation.