Background: The European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC) continues to recruit families with an increased risk of pancreatic cancer (PDAC) for both primary and secondary screening. Prospective risk of PDAC in families with multiple cases of the disease is sufficiently high to mean that they are suitable for screening for cancer, but most families have no known causative mutation. Some EUROPAC families have mutations in genes which cause cancer syndromes known to increase the risk of PDAC above the population baseline such as Hereditary Breast and Ovarian Cancer syndrome (BRCA1, BRCA2), Familial Atypical Mole Melanoma (p16, CDKN2A), Peutz Jeghers syndrome (STK11) and Lynch syndrome (HNPCC – MLH1, MSH2, MSH6, PMS2, EPCAM). However, the risk for mutation carriers taken as a whole is much less than would be predicted for prospective risk in families with multiple cases. This thesis addresses whether yield from screening can be improved by risk stratification and targeting screening to highest risk individuals. This includes addressing the hypothesis that a particular predisposing mutation may have different risks for cancer depending on the particular family history (context specific risk). Methods: Populations registered with EUROPAC were evaluated to allow description and comparison of individuals who attended for secondary screening with those who did not. Subsequently the population with confirmed pathogenic BRCA2 mutations was analysed to allow further description and to assess links between the familial risk of PDAC and other pheno-genetic characteristics. As part of the thesis a method was developed and optimised to allow full sequencing of the BRCA2 gene and surrounding bases to assess whether single-nucleotide variant (SNV) phenotypes may be linked to different cancer risks between BRCA2 families. This method included optimisation of cell plug formation, pulsed-field gel electrophoresis, quantitative PCR and Nanopore sequencing. Results: Participation in screening was found to be influenced by many factors including level of perceived risk. Lack of a specific mutation was a major element in reducing uptake, patients with known mutations perceived their risk as greater. However, the actual risk in BRCA2 carriers varied according to family history with individuals with fewer previous cases of PDAC in their family having risk that would probably not justify screening. From this we developed the hypothesis that whilst specific single mutations are necessary for an elevated risk of PDAC in some families, there are other factors that are necessary for these mutations to be penetrant. These other factors may be combinations of multiple polymorphisms in other genes, high risk combinations being ubiquitous in some families and absent in others. A method for carrying out long range haplotyping analysis was developed which can be taken forward to address this hypothesis.