Biomarkers of Gastric Premalignant Lesions

Excerpt

Gastric cancer is one of the most common and deadliest cancers worldwide. There is a significant diversity in risk and aggressiveness associated with the disease in terms of factors such as ethnicity, age, and diet. However, one thing that is common is the fact that infection with Helicobacter pylori (H. pylori) is often associated with the development of gastric adenocarcinoma. Infection with H. pylori induces a series of events that lead to non-atrophic gastritis (NAG), multifocal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia, and cancer. All the premalignant, proinflammatory stages are treatable, but it has been shown that the rate of progression to more advanced lesions is higher than the rate of regression. Most of the research efforts have focused on understanding the cancer stage, but there is still a large gap in the knowledge of biomarkers of the inflammatory stages and those of the progression/regression. Using samples from African American and Caucasian individuals with gastritis, we have been able to identify specific sets of single-nucleotide polymorphisms (SNPs) and haplotypes in cytokine genes associated with ethnicity. Interestingly, those same SNPs are also associated with advanced gastric lesions. On the other hand, using a cohort of Hispanic/Latino individuals with gastritis, we identified CD44 as a marker of disease progression and DMBT1 as a marker of disease aggressiveness. Both markers were validated in in vitro and in vivo systems.