Study of the interactions between environmental risk factors and germline genetic profiles in adrenocortical carcinoma
Aree / Gruppi di ricerca
Partecipanti al progetto
Descrizione del progetto
It has been shown that adrenocortical cancer (ACC) shares the somatic mutational signature typical of lung cancer and this implies a potential pathogenetic role for environmental factors. The aim of the project is to demonstrate what proportion of ACC is driven by germline mutations and whether exposure to environmental pollutants may synergize with genetic predisposition to facilitate ACC development. We will investigate the frequency of ACC in areas of our country with different degrees of pollution according to the official list by the Italian Department of Environment Clinical and demographic data of ACC patients will be captured in a web-based platform and analyzed to compare ACC frequency and outcome in polluted vs non-polluted areas. We will screen for known susceptibility genes by targeted NGS of leukocyte DNA in ACC patients banked samples. Results of gene profiling will be matched with clinical information to assess genotype-phenotype correlations. The project will provide data on the prevalence of ACC in Italy and new information on its pathogenesis. We will provide robust evidence on what amount of ACC is genetically determined and whether development of ACC may be promoted by environmental factors. The results of the present project will also contribute to elucidate mechanisms underlying the heterogeneity of ACC clinical course in terms of biological aggressiveness and response to treatment looking for relationships between environmental pollution genetic profiles and biological characteristics of the disease.