Universitą degli studi di Pavia

One of the aims of our research activity is the detection and the functional characterization of the genetic lesions associated with the development of gastrointestinal tumors in families with hereditary syndromes. These syndromes include HNPCC (hereditary non-polyposis colorectal cancer), FAP/MAP (familial adenomatous polyposis/MUTYH- associated polyposis) and HDGC (hereditary diffuse gastric cancer). Genetic testing of predisposition genes can establish the presence of cancer predisposing alterations or the absence of any specific changes. However, the finding of a variant of uncertain significance (often called VUS), is another possible result that can complicate rather than improve the risk assessment process. The functional significance of VUS is investigated by different approaches, including cell-based assays, in vitro and in silico analyses.
Findings from numerous studies have shown that the genetic component plays a crucial role not only in syndromic and familial cases, but also in the development of the so-called sporadic cancers. Genome Wide Association Studies (GWAS) have recently detected genetic variants at different loci that can modulate the risk of colorectal cancer. We are interested in investigating the functional significance of low-penetrance alleles that have been associated with an increased risk of colorectatal cancer; indeed, the association with risk is currently defined only at a statistic level. Functional significance is investigated by both in silico approaches and assessment of the expression of candidate genes.
Beside genetic factors predisposing to colorectal cancer, we are investigating the somatic lesions involved in colorectal cancer progression and development of metastases. The aim of the analysis is to identify possible prognostic markers that can be used in clinical practice.
Very recently, our group has started a collaborative study dealing with the genetic components associated with the pain treatment response in oncologic patients.