Abstract 4239: Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities

Abstract

Abstract Gastric cancer is a leading cancer health disparity among the Alaska Native (AN) people, occurring at a 3-fold higher incidence and 4-fold higher mortality rate in comparison to U.S. Non-Hispanic whites (NHW). AN gastric cancer patients have significant differences in tumor location and appearance compared to NHW patients. In addition, AN patients are younger at the time of diagnosis, 60 versus 69 years and have a lower 5-year survival rate of 10% compared to 22% of NHW gastric cancer patients. The purpose of this research was to understand the role of gene mutations, inflammation, and infection as possible factors in the promotion of gastric cancer in the AN population. In this study, we examined previously obtained tissue samples from AN gastric cancer patients diagnosed between 2006-2014 at the Alaska Native Medical Center. Using next-generation sequencing, immunohistochemistry and in situ hybridization, we evaluated for 50 cancer related gene mutations, the presence of the virus, Epstein-Barr virus (EBV), the bacterium, Helicobacter pylori (H. pylori), and inflammatory factors. Cancer related gene mutations were observed in 69% of gastric tumors from AN patients. The most commonly mutated genes were TP53 (30%), PIK3CA (13%), STK11 (6%), KRAS (5%), and PTEN (5%). Of particular interest, gene mutations were associated with patients who were younger at time of diagnosis (less than 55 years old) and had a history of chronic gastritis. Additionally, EBV is associated with 23% of AN gastric cancers, which is significantly higher than the 10% of EBV associated gastric cancer cases observed in other populations. EBV associated AN gastric cancer patients were more likely to have a history of chronic gastritis, prior or current H. pylori infection, and tobacco use. Notably, aberrant overexpression of the inflammatory factor cyclooxygenase 2 (COX-2) and the glycoprotein Mucin 1 (MUC1) in gastric cancer cells was significantly associated with a poorer prognosis among AN gastric cancer patients. Collectively, these findings indicate infection and inflammation are potential driving factors in the pathogenesis of gastric cancer among the AN people, which may have important clinical implications. Citation Format: Holly Martinson, Steven Alberts, Matthew Olnes. Infection, inflammation and cancer: Understanding Alaska Native cancer health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4239.