Autoimmune Diseases and Gastric Cancer Risk: A Systematic Review and Meta-Analysis

Autoimmunity is an alternative etiology of gastric inflammation, the initiating event in the gastric carcinogenic cascade. This mechanism may be an increasingly important cause of gastric cancer with the waning prevalence of its primary etiologic factor, chronic Helicobacter pylori infection.

PubMed and EMBASE were searched up to September 2018. Autoimmunity and 96 specific manifestations were considered for associations with gastric cancer risk. Random effects analysis was used to calculate pooled relative risk estimates (RR) and 95% confidence intervals (CI).

We found a total of 52 observational studies representing 30 different autoimmune diseases. Overall, the presence of an autoimmune condition was associated with a gastric cancer pooled RR of 1.37 (95% CI, 1.24 to 1.52). Among the 24 autoimmune conditions with two or more independent reports, nine were significantly associated with increased gastric cancer risk: dermatomyositis (RR, 3.69; 95% CI, 1.74 to 7.79), pernicious anemia (RR, 2.84; 95% CI, 2.30 to 3.50), Addison disease (RR, 2.11; 95% CI, 1.26 to 3.53), dermatitis herpetiformis (RR, 1.74; 95% CI, 1.02 to 2.97; n=3), IgG4-related disease (RR, 1.69; 95% CI, 1.00 to 2.87), primary biliary cirrhosis (RR, 1.64; 95% CI, 1.13 to 2.37), diabetes mellitus type 1 (RR, 1.41; 95% CI, 1.20 to 1.67), systemic lupus erythematosus (RR, 1.37; 95% CI, 1.01 to 1.84), and Graves disease (RR, 1.27; 95% CI, 1.06 to 1.52).

Our analysis documents the wide range of autoimmune diseases associated with gastric cancer. These associations may reflect unreported links between these conditions and autoimmune gastritis. Further studies are warranted to investigate potential causal mechanisms.