Abstract 5051: Associations between autoimmune conditions and gastric cancer risk among elderly US adults

Background: The associations of multiple autoimmune conditions with gastric cancer may reflect their co-occurrence with autoimmune gastritis and its clinical manifestation pernicious anemia (PA), known risk factors for this malignancy. We analyzed diagnoses in US elderly aged >65 years to investigate the spectrum of these associations and the extent of mediation by PA. Methods: We conducted a population-based nested case-control study using the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. 35,499 gastric cancer cases first diagnosed in SEER during 1992-2013 were compared to 200,000 cancer-free controls matched by age, sex and year of selection from a 5% random sample of Medicare beneficiaries. Autoimmune conditions were identified from inpatient Medicare claims. Logistic regression models estimated associations between autoimmune conditions and gastric cancer, as well as their direct and indirect effects on cancer risk. Results: Among 40 autoimmune conditions evaluated, four were associated with increased gastric cancer risk (odds ratio, 95% confidence interval): autoimmune hepatitis (3.32, 1.30-8.50), PA (1.94, 1.81-2.08), uveitis (1.33, 1.03-1.70) and pure red cell aplasia (1.30, 1.09-1.54). Amyotrophic lateral sclerosis was associated with decreased risk (0.23, 0.06-0.96), based on 2 gastric cancer cases vs. 47 controls with this diagnosis. Within the control population, PA was positively associated with eight other autoimmune conditions: aplastic anemia (4.45, 2.47-8.35), Crohn’s disease (3.61, 2.48-5.25), pure red cell aplasia (2.83, 2.03-3.95), polymyositis/dermatomyositis (2.82, 1.34-5.95), celiac disease (2.51, 1.24-5.08), Addison disease (2.17, 1.32-3.56), rheumatoid arthritis (1.75, 1.53-2.01) and ulcerative colitis (1.57, 1.07-2.31). Mediation analysis indicated that PA may account for 20% (p=6.52E-09) of pure red cell aplasia’s effect on gastric cancer risk. PA failed to show significant mediation of the effects of autoimmune hepatitis, uveitis and amyotrophic lateral sclerosis. Conclusions: Our study confirmed previously reported associations of PA and several other autoimmune conditions with gastric cancer risk. The association that we found between pure red cell aplasia and gastric cancer was partially mediated by PA. We also identified an intriguing set of autoimmune conditions associated with PA, many of which have been previously linked to gastric cancer; their lack of association with cancer in our data may be due to low population prevalence and insufficient statistical power. The relatively small fraction of mediation by PA does not preclude a more substantial role of subclinical autoimmune gastritis in gastric cancer etiology. Alternatively, autoimmunity may contribute through a different mechanism, perhaps via aggravation of mucosal infection by Helicobacter pylori. Citation Format: Minkyo Song, M. Constanza Camargo, Andriy Derkach, Eric A. Engels, Charles S. Rabkin. Associations between autoimmune conditions and gastric cancer risk among elderly US adults [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5051.