SLE, Other Autoimmune Diseases Linked With Gastric Cancers

Systemic lupus erythematosus (SLE) is 1 of 6 autoimmune disorders that appears to be associated with an increased risk of gastric cancer, according to a major new meta-analysis involving hundreds of thousands of patients.

The study, published in Frontiers in Immunology, could help bring clarity to the question of whether and how gastric cancers and autoimmune disorders are linked.

Corresponding author József Czimmer, MD, PhD, of the University of Pécs, in Hungary, and colleagues, explained that gastric cancers have a high mortality rate, making them an area urgently in need of research. The average 5-year survival rate is just 20%.

Efforts to eradicate Helicobacter pylori infection, which has been shown to be a causative factor for gastric cancers, have been effective. Yet, Czimmer said the cancer remains the fifth-most-prevalent cancer in the world. One possible reason for the persistence of the cancer type, the authors said, is the increase in rates of autoimmune diseases. Autoimmune gastritis is believed to be the cause of 7.8% to 19.5% of cases of gastric cancer.

“An increase in the incidence of autoimmune diseases has been observed recently parallelly with the increasing incidence of cancers,” the authors said. “The autoimmune inflammation often correlates with the tumorous disorder of the affected organ.”

Still, the investigators said the causal links between autoimmune gastritis and gastric cancer remain controversial. In light of the disagreement, the authors set out to perform a meta-analysis in hopes of making clear the connections (or lack thereof) between the 2 types of diseases.

Czimmer and colleagues conducted a systematic literature review that included studies investigating incidences of gastric cancer in autoimmune disorders. They found 43 articles, which were conducted on 4 continents and included a total of 499,427 patients. Using those reports, the authors calculated standardized incidence ratios (SIR) with 95% confidence intervals (CI).

Of the 36 autoimmune disorders covered by the studies, the authors found statistically significant correlations between gastric cancers and 6 of the disorders: dermatomyositis (SIR = 3.71; 95% CI, 2.04-6.75), pernicious anemia (SIR = 3.28; 95% CI, 2.71, 3.96), inflammatory myopathies (SIR = 2.68; 95% CI, 1.40-5.12), SLE (SIR = 1.48; 95% CI, 1.09-2.01), diabetes mellitus type I (SIR = 1.29; 95% CI, 1.14-1,47), and Graves’ disease (SIR = 1.28; 95% CI, 1.16-1.41).

Though the study appears to affirm a correlation between autoimmune diseases and gastric cancer, the precise causal links remain unclear. However, Czimmer and colleagues laid out some possible reasons.

“Several common factors can be identified, such as immunosuppression/dysregulation, infections, dietary habits, environmental factors, and chronic inflammation,” they wrote. “These factors can induce chronic cell damage and can trigger either autoimmune conditions or cancer.”

The authors added that autoimmune disorders may also lead to antigen specificity-driven tissue damage, which in turn can lead to inflammation, leading to carcinogenesis.

The authors said their study’s strength is its large scope and the large number of studies included. However, they also noted that there are other potential causes of gastric cancer that were not reported or analyzed in their meta-analysis.

Still, they said the apparent associations they found suggest patients with the 6 autoimmune disorders warrant close monitoring by physicians for potential cancer.

“For clinical practice, close gastroenterological follow-up or routinely performed gastroscopy and application of other diagnostic measures may be cost-effective and clinically helpful for patients diagnosed with these six autoimmune diseases,” the authors concluded. “Based on the importance of the problem, conducting further clinical trials on this topic is essential.”

Reference

Zádori N, Szakó L, Váncsa S, et al. Six autoimmune disorders are associated with increased incidence of gastric cancer: A systematic review and meta-analysis of half a million patients. Front Immunol. 2021;12:750533. Published 2021 Nov 23. doi:10.3389/fimmu.2021.750533