Risk Factors and Incidence of Gastric Cancer After Detection of Helicobacter pylori Infection: A Large Cohort Study

Abstract

Background & aims: Nearly all studies of gastric adenocarcinoma in the United States have relied on national cancer databases, which do not include data on Helicobacter pylori infection, the most well-known risk factor for gastric cancer. We collected data from a large cohort of patients in the United States to calculate the incidence of and risk factors for nonproximal gastric adenocarcinomas after detection of H pylori. Secondary aims included identifying how treatment and eradication affect cancer risk.

Methods: We performed a retrospective cohort study, collecting data from the Veterans Health Administration on 371,813 patients (median age 62 years; 92.3% male) who received a diagnosis of H pylori infection from January 1, 1994, through December 31, 2018. The primary outcome was a diagnosis of distal gastric adenocarcinoma 30 days or more after detection of H pylori infection. We performed a time to event with competing risk analysis (with death before cancer as a competing risk).

Results: The cumulative incidence of cancer at 5, 10, and 20 years after detection of H pylori infection was 0.37%, 0.5%, and 0.65%, respectively. Factors associated with cancer included older age at time of detection of H pylori infection (subhazard ratio [SHR], 1.13; 95% confidence interval [CI], 1.11-1.15; P < .001), black/African American race (SHR, 2.00; 95% CI, 1.80-2.22), Asian race (SHR, 2.52; 95% CI, 1.64-3.89) (P < .001 for race), Hispanic or Latino ethnicity (SHR, 1.59; 95% CI, 1.34-1.87; P < .001), and history of smoking (SHR, 1.38; 95% CI, 1.25-1.52; P < .001). Women had decreased risk of gastric adenocarcinoma compared with men (SHR, 0.52; 95% CI, 0.40-0.68; P < .001); patients whose H pylori infection was detected based on serum antibody positivity also had a reduced risk of cancer (SHR 0.74; 95% CI, 0.54-1.04; P = .04). Patients who received treatment for their H pylori infection still had an increased risk of gastric cancer (SHR, 1.16; 95% CI, 0.74-1.83; P = .51) but confirmed H pylori eradication after treatment reduced risk of gastric cancer (SHR, 0.24; 95% CI, 0.15-0.41; P < .001).

Conclusions: In a study of 371,813 veterans with a diagnosis of H pylori infection, we found significantly higher risks of gastric cancer in racial and ethnic minorities and smokers. Treatment of H pylori infection decreased risk only if eradication was successful. Studies are needed on the effects of screening high-risk persons and to identify quality measures for diagnosis, resistance patterns, and treatment efficacy.

Keywords: Antibacterial Therapy; Microbe; Screening; Stomach Cancer.

Figure 1a–c:

Cohort of patients: a) with H pylori; b) who developed non-proximal gastric adenocarcinoma; and c) among those a positive diagnostic test (endoscopic pathology, stool antigen, urea breath test) who underwent treatment and eradication testing ICD = International Classification of Diseases (administrative codes)

Figure 2a–d:

Cumulative incidence curves for a) race; b) ethnicity; c) gender; d) method of H pylori diagnosis, amongst entire cohort, adjusted for other covariates RX = prescription therapy; ICD = International Classification of Diseases (administrative codes); Ab = antibody

Figures 3a–d:

plotted sub-hazard ratios for development of gastric cancer after positive diagnostic test (endoscopic pathology, stool antigen, urea breath test), considering a) treatment status and b) eradication status, and cumulative incidence curves for c) treatment of H pylori and d) eradication of H pylori, adjusted for other covariates HR = hazard ratio