Evaluation of serum antibodies to Helicobacter pylori proteins and hepatobiliary cancers
Principal Investigator
Name
Gwen Murphy
Degrees
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Institution
Imperial College London
Position Title
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Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
2013-0035
Initial CDAS Request Approval
Mar 4, 2013
Title
Evaluation of serum antibodies to Helicobacter pylori proteins and hepatobiliary cancers
Summary
Helicobacter pylori (H. pylori) is a gram negative bacteria which can colonize the stomach and is a strong risk factor for ulcer and gastric cancer. Other helicobacter species may also be important for health and a growing body of literature supports a possible role of Helicobacter species (spp) in extragastric cancers, and in hepatobiliary cancers specifically.
Hepatobiliary cancers are the second leading cause of cancer-related mortality worldwide and have very poor five-year survival. H. pylori and likely other Helicobacter spp are amenable to antibiotic intervention, such that a causal association between Helicobacter spp and hepatobiliary cancers is of potential public health importance. We have recently found a statistically significant increase in risk of biliary cancer for individuals seropositive for antibodies to a number of H. pylori proteins in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Although the prevalence of H. pylori infection was also higher in liver cancer cases, relative to controls, the association became attenuated after a multivariate adjustment. In contrast, we found that individuals who were seropositive for antibodies to a combination of four H. pylori proteins (GroEL, UreA, HP0305 and Omp) had a ninefold increase in risk of biliary cancer relative to those we were seronegative for all four. This is a novel finding, and we are looking to replicate it in the high quality prospectively collected samples of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
We propose, therefore, to assess whether seropositivity to antibodies against 23 H. pylori proteins is associated with subsequent risk of hepatobiliary cancer using serum samples from 186 cases (n=107 liver, n=27 gallbladder and n=52 other biliary cancer cases) and matched controls in PLCO.
Hepatobiliary cancers are the second leading cause of cancer-related mortality worldwide and have very poor five-year survival. H. pylori and likely other Helicobacter spp are amenable to antibiotic intervention, such that a causal association between Helicobacter spp and hepatobiliary cancers is of potential public health importance. We have recently found a statistically significant increase in risk of biliary cancer for individuals seropositive for antibodies to a number of H. pylori proteins in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Although the prevalence of H. pylori infection was also higher in liver cancer cases, relative to controls, the association became attenuated after a multivariate adjustment. In contrast, we found that individuals who were seropositive for antibodies to a combination of four H. pylori proteins (GroEL, UreA, HP0305 and Omp) had a ninefold increase in risk of biliary cancer relative to those we were seronegative for all four. This is a novel finding, and we are looking to replicate it in the high quality prospectively collected samples of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
We propose, therefore, to assess whether seropositivity to antibodies against 23 H. pylori proteins is associated with subsequent risk of hepatobiliary cancer using serum samples from 186 cases (n=107 liver, n=27 gallbladder and n=52 other biliary cancer cases) and matched controls in PLCO.
Aims
Based on our previous results, we hypothesize that seropositivity of antibodies against H. pylori proteins will be associated with biliary cancers, and may be associated with liver cancer. We propose to measure seropositivity to antibodies against 23 H. pylori proteins in baseline serum from 186 hepatobiliary cases and 372 age- and sex- matched controls in PLCO.
Collaborators
Katherine McGlynn (DCEG, HREB)
Jill Koshiol (DCEG, IIB)
Neal Freedman (NCI)
Gwen Murphy (NCI, DCEG, NEB)
Related Publications
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Helicobacter hepaticus and Helicobacter bilis in liver and biliary cancers from ATBC and PLCO.
Murphy G, Freedman ND, Abnet CC, Albanes D, Cross AJ, Huang WY, Koshiol J, McGlynn K, Parisi D, Männistö S, Weinstein SJ, Waterboer T, Butt J
Helicobacter. 2024; Volume 29 (Issue 1): Pages e13053 PUBMED -
Seropositivity for Helicobacter pylori and hepatobiliary cancers in the PLCO study.
Makkar R, Butt J, Huang WY, McGlynn KA, Koshiol J, Pawlita M, Waterboer T, Freedman ND, Murphy G
Br. J. Cancer. 2020 Sep; Volume 123 (Issue 6): Pages 909-911 PUBMED