Oesophageal and Proximal Gastric Adenocarcinomas Are Rare After Detection of Helicobacter pylori Infection

Shria Kumar; David C. Metz; Gregory G. Ginsberg; David E. Kaplan; David S. Goldberg

Disclosures

Aliment Pharmacol Ther. 2020;51(8):781-788. 

In This Article

Abstract and Introduction

Abstract

Background: Helicobacter pylori infection is the most important risk factor for non-proximal gastric adenocarcinoma, yet some posit it is protective against oesophageal adenocarcinoma and proximal gastric cancers.

Aims: To evaluate the incidence of and risk factors for future oesophageal and proximal gastric cancers, utilizing the largest North American cohort of patients with previously identified H pylori. Also to identify whether treatment and eradication of H pylori alter future oesophageal and proximal gastric cancer risk.

Methods: Retrospective cohort study within the Veterans Administration of 36 803 patients (median age 60.4 years; 91.8% male) with confirmed H pylori between 01 January 1994 and 31 December 2018. Primary outcome was diagnosis of future oesophageal and proximal gastric cancers. A time to event with competing risk analysis was performed, evaluating patient factors and whether the patient received H pylori treatment. Secondary analysis of those treated evaluated whether confirmed eradication was associated with cancer.

Results: The cumulative incidence of oesophageal and proximal gastric cancers 5, 10 and 15 years after H pylori detection was 0.145%, 0.26% and 0.34%. Risk of future oesophageal or proximal gastric cancer was similar amongst whites (reference), African Americans (SHR 0.87, 95%CI 0.57–1.43) and American Indians (SHR 1.31, 95%CI 0.18–9.60) but substantially reduced in those of Asian (no cases amongst 213 H pylori positive) or native Hawaiian origin (no cases amongst 295 H pylori positive) (P < .001). Increasing age (SHR 1.17 per 5 years, 95% CI: 1.09–1.25, P < 0.001) and smoking (SHR 2.06, 95% CI: 1.33–3.18, P = 0.001) were associated with oesophageal and proximal gastric cancers. Neither treatment of H pylori nor eradication status were associated with cancer (P > 0.20).

Conclusions: In the largest study of US patients with H pylori, we demonstrate that rates of oesophageal and proximal gastric cancers after treatment of H pylori are low. Older age, and smoking are associated with future cancer, whilst Asian or Native Hawaiian race are protective. H pylori treatment and eradication are not associated with future cancer.

Introduction

Helicobacter pylori is an established risk factor for non-cardia gastric cancers, with the World Health Organization labelling it a class 1 carcinogen.[1–3] Consensus guidelines within the US recommend eradication of H pylori when detected, using a multi-drug antibiotic regimen and subsequent re-testing for confirmation of eradication.[4] In countries with high prevalence of both H pylori and gastric cancer, such as Japan, H pylori eradication is a public health initiative, in order to decrease cancer-related mortality.[5–7] Yet despite its class 1 carcinogenic status, mass eradication of H pylori is not without controversy. Those who argue against mass eradication of H pylori point out a number of factors: antibiotic resistance, antibiotic associated diseases, and the risk of oesophageal and proximal (cardia) adenocarcinomas.[8–14]

There have been a number of studies investigating the inverse relationship between oesophageal adenocarcinoma and proximal stomach adenocarcinoma, both in the US, other Western countries, and Eastern countries such as Japan and China (where the incidence of oesophageal adenocarcinoma is lower).[8,10,11] The predominant hypothesis is that with improved sanitation conditions, there has been a decrease in H pylori prevalence during the past century, particularly in Western countries: this change in microbiota has paralleled lower rates of non-cardia cancer and higher rates of cardia cancer.[8,15] However, the evidence for this inverse relationship is not uniformly agreed upon, and therefore H pylori's importance in oesophageal and proximal gastric cancers remains unclear.[16–18] This controversy also poses a dilemma for the management of H pylori treatment, and whether eradication of H pylori should be reconsidered in particular groups.

To address this knowledge gap, we sought to determine the relationship between H pylori and subsequent oesophageal and proximal gastric cancers in order to help guide nuanced H pylori treatment, to maximise benefit while minimizing harm. We evaluate the incidence of and risk factors for future oesophageal and proximal gastric cancers, utilizing the largest North American cohort of patients with previously identified H pylori.[19] We also identify whether treatment and eradication of H pylori alter future oesophageal and proximal gastric cancers risk.

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