Examination of intraductal papillary mucinous neoplasms of pancreas and their association with extrapancreatic malignancies

Abstract

The primary objective of the thesis is to assess the prevalence and the incidence of extrapancreatic malignancies (EPMs) in a cohort of Italian patients diagnosed with intraductal papillary mucinous neoplasms (IMPNs) of pancreas, and to identify the risk factors for their occurrence. The secondary objective is to assess an association between pancreatic IPMN and selected single nucleotide polymorphisms (SNPs) within 8q24 region of human genome. The tertiary objective of the thesis is to assess whether patients with pancreatic IPMNs have an increased propensity to develop colorectal adenomas. Methods: In order to meet the objectives three separate studies were conducted: the hospital-based multicentric study, the genetic association study and the colonoscopic case-control study. The hospital-based multicentric study was conducted in Italy from January 2010 to January 2011 in eight participating centers. Three hundred ninety IPMN cases were included in the study and screened for EPMs. EPMs were grouped according to time of their diagnosis as previous, synchronous (both prevalent) and metachronous (incident). The distribution of demographics, medical history and lifestyle habits was assessed among cases. The observed/expected (O/E) ratio of prevalent EPMs was calculated. The genetic association study was performed on 117 IPMN cases and 231 age and gender matched controls. Cases were enrolled at the Digestive Endoscopy Unit, Policlinico Agostino Gemelli, Rome, Italy with either a prevalent or incident IPMN diagnosis, diagnosed from January 2010 to June 2011. Status of selected SNPs (rs6983267, rs6993464, rs7014346, rs10505477) was determined using a StepOne Realtime PCR system (Applied Biosystems) and TaqMan SNP Genotyping Assay ™ 40X. Unconditional multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of selected SNPs and IPMNs...