Seropositivity for Helicobacter pylori and hepatobiliary cancers in the PLCO study

Rishi Makkar,Jill Koshiol,Katherine A Mcglynn,Gwen Murphy,Michael Pawlita,Neal D Freedman,Tim Waterboer,Wen-Yi Huang,Julia Butt

doi:10.1038/s41416-020-0961-0

Abstract

Helicobacter has been suggested to play a possible role in hepatitis, gallstones, and hepatobiliary tumours. We assessed whether seropositivity to 15 H. pylori proteins was associated with subsequent incidence of 74 biliary tract and 105 liver cancer cases vs. 357 matched controls in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Odds ratios and 95% confidence intervals were computed by conditional logistic regression after adjustment for known hepatobiliary cancer risk factors. H. pylori seropositivity was not associated with either biliary tract (1.76, 0.90–3.46) or liver cancer (0.87, 0.46–1.65). CagA seropositivity was associated with both endpoints, although the latter association was not statistically significant (biliary tract: 2.16, 1.03–4.50; liver cancer: 1.96, 0.98–3.93) and neither association was statistically significant after correcting for multiple comparisons. Together, these results suggest possible associations between H. pylori and hepatobiliary cancer and suggest the value of future studies investigating the association.Trial registration number: NCT00339495.

Highlights

Helicobacter pylori is a known risk factor for peptic ulcer disease and gastric cancer
We previously observed an association between H. pylori and subsequent incidence of biliary cancer (odds ratio (OR): 5.47, 95% confidence interval (CI): 1.17, 25.65) in the Finnish Alpha Tocopherol, Beta Carotene Cancer (ATBC) Prevention Study,[14] with associations observed for seropositivity to the UreaA, Omp, HP0231, and HP0305 antigens
Seropositivity to H. pylori was not associated with either biliary tract (OR: 1.76, 95% CI: 0.90, 3.46) or liver cancer (OR: 0.87, 95% CI: 0.46. 1.65) overall or by subsite: gallbladder (OR: 1.56, 95% CI: 0.43, 5.66), extrahepatic bile duct (OR: 2.94, 95% CI: 0.87, 9.89), ampulla of vater (OR: 1.71, 95% CI: 0.30, 9.82), intrahepatic bile duct (OR: 1.15, 95% CI: 0.27, 4.96), or hepatocellular carcinoma (OR: 0.93, 95% CI: 0.45, 1.93)

Summary

Introduction

Helicobacter pylori is a known risk factor for peptic ulcer disease and gastric cancer. Previous studies have suggested a role for H. pylori and other Helicobacter species in the incidence of hepatobiliary cancers.[1,2,3] Cross-sectional studies have found evidence for H. pylori in liver[4,5,6] and biliary tissue[7] as well as in bile.[8,9] Animal studies have shown that Helicobacter infections can cause hepatitis, gallstones, and liver cancer.[10,11,12,13] Yet, few prospective studies have been conducted. We previously observed an association between H. pylori and subsequent incidence of biliary cancer (odds ratio (OR): 5.47, 95% confidence interval (CI): 1.17, 25.65) in the Finnish Alpha Tocopherol, Beta Carotene Cancer (ATBC) Prevention Study,[14] with associations observed for seropositivity to the UreaA, Omp, HP0231, and HP0305 antigens

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