• polymorphisms
• pancreatic cancer
• eQTLs
• susceptibility risk loci

Pancreatic ductal adenocarcinoma (PDAC), which represent the 95% of all the pancreatic cancers, is one among the most lethal cancer, associated with a very poor prognosis for which incidence closely parallels mortality. The 5-year survival in patients with pancreatic cancer remains low but is slightly increasing from 5% up to 10% in the last years. The poor prognosis is mostly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage. Consequently, the prevention or diagnosis at early stages is extremely difficult and would be very important to achieve. At present, the strongest known risk factors for pancreatic cancer are family history, chronic pancreatitis, type 2 diabetes mellitus and cigarette smoking.
In the last years Genome-Wide Association Studies (GWAS) have been used as a powerful tool for detecting many genetic variants that underlie phenotypic variation of complex traits in population-based samples. Epidemiologic evidences suggest single nucleotide polymorphisms (SNPs) as the most common genetic variants linked to cancer susceptibility. However, the search for more loci is of the uttermost importance, and it would be especially beneficial for SNPs with a functional effect on gene function or gene expression regulation. Many human traits are affected by alterations in gene expression. We have hypothesized that genetic variation that has an effect on the expression of genes expressed in pancreatic tissue could also have an impact on the susceptibility of developing PDAC. As the purpose of this thesis work, we have investigated the associations between polymorphisms affecting gene function in the pancreas, the so-called “expression quantitative trait loci” (eQTLs), and PDAC risk.