Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Epstein-Barr virus infection and immunologic dysfunction in patients with aqueous tear deficiency

The authors tested their hypothesis that Epstein-Barr virus (EBV) infection is a risk factor for aqueous tear deficiency (ATD) by evaluating 38 ATD patients and 17 controls for serologic evidence of EBV infection. Aqueous tear deficiency was graded clinically as mild or severe. A linear trend toward elevated EBV capsid (P less than 0.05) and early antigen (P less than 0.001) titers was noted from control to severe ATD patients. Rubella and cytomegalovirus antibody titers were poorly correlated with EBV titers, suggesting that the elevated EBV antibodies in ATD patients were not due to nonspecific polyclonal B-cell activation. Epstein-Barr virus antigens were detected in two of six lacrimal gland biopsies from severe ATD patients with Sjögren\u27s syndrome, but in none of the control glands. Aqueous tear deficiency patients were evaluated for immunologic dysfunction associated with EBV infection. Linear trends of elevated serum IgG (P less than 0.05), autoantibody and immune complex positivity (P less than 0.05), and reduced natural killer cell cytotoxicity (P less than 0.05) were found from controls to severe ATD patients. Furthermore, reduced T-helper lymphocyte counts (P less than 0.06) and an increased percentage of HLA-DR+ CD8 lymphocytes (P less than 0.05) were observed in severe ATD patients compared with the mild and control groups. A multivariate analysis of the data showed a significant correlation between severe ATD and elevated EBV early antigen titers, Sjögren\u27s syndrome, and an increased percentage of HLA-DR+ CD8 lymphocytes. The authors\u27 findings suggest that EBV infection may be a risk factor for development of ATD in a subset of ATD patients with greater disease severity, Sjögren\u27s syndrome, and immunologic dysfunction