Our studies are focused on the mechanisms responsible for the development of cancer associated to bacterial infection using the model system of Helicobacter pylori and gastric cancer. Gastric cancer remains the third cause of cancer-related death and is still a major public health concern. It is often associated with a bad prognosis with a 5 years survival rate of 15 to 20% in countries such as France. Epidemiological studies have clearly established that Helicobacter pylori infection is the major risk factor for gastric cancer. H. pylori infects half of the worldwide population and induces a chronic gastritis. Only a subset of H. pylori-infected people (1 to 3%) will develop gastric neoplasia. Gastric cancer is an inflammation-driven disease resulting from a multifactorial process including H. pylori virulence factors, host genetic context and factors related to life habits as diet.
Genetic instabilities and epigenetic modifications are among the earliest events in cancer process, triggered by inflammation. Our previous studies showed that H. pylori has a mutator effect at the nuclear and mitochondrial genome and impairs host DNA damage repair systems. Our aims are to characterize molecular events at the origin of the genotoxic activity of H. pylori infection and its oncogenic consequences. We develop two main projects focused on the study of pleiotropic transcriptional regulators, Upstream Stimulating factors (USF) and their involvement in the host response to the infection. These USF factors have been previously demonstrated as stress sensors and would be associated with a tumor suppressive activity. In order to identify host factors that play an important role in the pathogenicity associated to H. pylori infection, we also investigate the consequences of H. pylori at mitochondria of which dysfunctions are associated with several human diseases including cancer. Our work is specially focused on mitochondrial genome and mechanisms related to maintenance of its integrity during the infection.
In a second part of our projects, we develop a translational approach in collaboration with clinicians to characterize biomarker candidates and methods for an early detection of gastric cancer. Such methods could also allow an adapted follow-up for the patients. This is of special public health concern, leading to reduce the mortality and morbidity rates of gastric cancer.