Abstract IA06: Understanding the molecular landscape of gastric premalignant lesions
Authors: Garai Jone , Piazuelo Maria B. , Camargo Maria C. , Correa Pelayo , Wilson Keith , Zabaleta Jovanny 
Published: August 2020

Even though the incidence of gastric cancer has been declining over the years, it still has a very high mortality rate. The incidence and mortality of gastric cancer is, however, significantly higher in minority populations with African Americans and Hispanic individuals presenting 52% and 43%, respectively, more cases than Caucasians (data for male patients). Gastric adenocarcinoma has been strongly associated to infection with Helicobacter pylori (H. pylori). The infection triggers an inflammatory cascade, known as the Correa's cascade, that changes the normal gastric epithelium into nonatrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. It is known that these events involve immune infiltration and damage to the gastric mucosa; however, there is still too much to learn about the gastric premalignant stages and the evolution of them over time. Over the years we have identified single-nucleotide polymorphisms (SNPs) and differential expression of genes associated with premalignant stages and with evolution of the disease over time. We found that African Americans have increased incidence of advanced premalignant lesions and have more prevalence of infection with H. pylori than Whites. In addition, we found that SNPs and haplotypes in the interleukin 1 b gene (IL1B) are associated with advanced gastritis in African American individuals. Interestingly, the frequency of these inflammatory SNPs and haplotypes is different among African American and Caucasian individuals. In terms of gene expression, we have also found that the increased expression of the gene deleted in malignant brain tumors 1 (DMBT1) is associated with the development of advanced gastritis while the expression of CD44 is associated with progression of the disease over time. Given that CD44 is a molecule involved in the homing of inflammatory cells, its association with progression of premalignant stages over time highlights the role of the immune response in the outcome of these lesions. Interestingly, these immune responses seem to be also modulated by H. pylori itself. We have shown that H. pylori components are able to modulate acquired and innate immune responses. In addition, we have also found a microRNA pattern associated with advanced premalignant gastric lesions in both African Americans and Caucasians. Understanding the molecular landscape of the gastric lesions may help us devise strategies to intervene and limit their progression into more advanced lesions, including gastric cancer.

Citation Format: Jone Garai, Maria B. Piazuelo, Maria C. Camargo, Pelayo Correa, Keith Wilson, Jovanny Zabaleta. Understanding the molecular landscape of gastric premalignant lesions [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA06.