Gastric cancer, one of the most common types of cancer, is associated with high mortality rates. In the last decades, a decrease in the worldwide incidence has been observed with some changes in the therapeutic and diagnostic options.
However, the prognosis for this disease still remains poor, mainly when the diagnosis is performed at advanced stages. The therapy most effective is still surgical resection and in a significant number of cases, especially in the advanced stage, it is only palliative. Thus, it is of extreme importance to study the mechanisms that act in gastric carcinogenesis and research possible markers that can assist in earlier diagnosis.
Helicobacter pylori (H. pylori) is one of the more important etiological factors in gastric cancer, especially in those who have the cagA gene in their genome. In addition to the accepted role of H. pylori in the pathogenesis of gastric cancer, the Epstein Barr virus (EBV) has been associated with gastric cancer. DNA methylation is an epigenetic modification found in many physiological events, however, when it is aberrant it has been identified as being associated with inactivation of tumor suppressor genes.
Microsatellite instability (MSI) reflects an erroneous form of DNA replication in repetitive microsatellite sequences and has been considered a hallmark of DNA mismatch repair gene inactivation and therefore consequently leads to genetic instability. Some studies have linked DNA hypermethylation and MSI with H. pylori-cagA+ and EBV infection but these data are not conclusive and the studies did not examine both agents at the same time.
A study by Ferrasi et al, has recently been published on January 21, 2010 in World Journal of Gastroenterology, analyzed samples of gastric cancer (diffuse and intestinal type) for both etiological factors and correlated them with genetic (MSI) and epigenetic (methylation) alterations as well as with clinical and epidemiological data. Five genes were analyzed for methylation status: CDH1, COX2, hMLH1, CDKN2A and DAPK. The findings of this research are important as they suggest an association between H. pylori-cagA+ infection and silencing of the CDH1 gene. This gene encodes the E-cadherin protein that is very important in preventing metastasis.