Autoimmune Disease and Subsequent Risk of Developing Alimentary Tract Cancers Among 4.5 Million US Male Veterans

BACKGROUND: Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer. METHODS: On the basis of 4,501,578 US male veterans, the authors identified 96,277 men who developed alimentary tract cancer during up to 26.2 years of follow-up. By using Poisson regression methods, the authors calculated relative risks (RRs) and 95% confidence intervals. RESULTS: A history of autoimmune disease with localized alimentary tract effects generally increased cancer risks in the organ(s) affected by the autoimmune disease, such as primary biliary cirrhosis and liver cancer (RR, 6.01; 95% confidence interval [Cl], 4.76-7.57); pernicious anemia and stomach cancer (RR, 3.17; 95% Cl, 2.47-4.07); and ulcerative colitis and small intestine, colon, and rectal cancers (RR, 2.53; 95% Cl, 1.05-6.11; RR, 2.06; 95% Cl, 1.70-2.48; and RR, 2.07; 95% Cl, 1.62-2.64, respectively). In addition, a history of celiac disease, reactive arthritis (Reiter disease), and systemic sclerosis all were associated significantly with increased risk of esophageal cancer (RR, 1.86-2.86). Autoimmune diseases without localized alimentary tract effects generally were not associated with alimentary tract cancer risk, with the exception of decreased risk for multiple alimentary tract cancers associated with a history of multiple sclerosis. CONCLUSIONS: These findings support the importance of localized inflammation in alimentary tract carcinogenesis. Future research is needed to confirm the findings and improve understanding of underlying mechanisms by which autoimmune diseases contribute to alimentary tract carcinogenesis. Cancer 2011;117:1163-71. Published 2010 by the American Cancer Society*