review of literature on clinical pancreatology - The Pancreapedia

patients from the Swedish Hospital Discharge Register and linking them with the NationalCancer Registry. Follow-up <strong>of</strong> patients was carried out from the last hospitalisation through2004. A total <strong>of</strong> 15 858 patients were hospitalised for psoriasis during 1965-2004, <strong>of</strong> whom1408 developed cancer, giving an overall standardised incidence ratios (SIRs) <strong>of</strong> 1.33. Asignificant excess was noted for squamous cell skin cancer, and for cancers <strong>of</strong> the upperaerodigestive tract, oesophagus, stomach, liver, pancreas, lung, kidney and bladder as wellas non-Hodgkin lymphoma. Many <strong>of</strong> these may reflect the effects <strong>of</strong> alcohol drinking andtobacco smoking [353].Genetic aspectsPancreatic cancer, like many other complex diseases, has genetic and environmentalcomponents to its etiology. It is likely that relatively common genetic variants with modesteffects on pancreatic cancer risk play an important role in both familial and sporadic forms <strong>of</strong>the disease, either individually or in interaction with environmental factors. The relatively highfrequency <strong>of</strong> such variants means that they could potentially explain a substantial portion <strong>of</strong>disease risk. In general, very few low-penetrance variants have been identified and thosethat have require replication in independent studies. Possible gene-environment interactionsarising from these studies also require replication. More comprehensive approaches areneeded to make progress, including global analyses <strong>of</strong> biologically sound pathways andgenome-wide association studies. Large sample sizes are required to do this appropriatelyand multi-study consortia make this possible. A number <strong>of</strong> consortia <strong>of</strong> pre-existing studieshave already been formed, and these will facilitate the identification <strong>of</strong> further low-penetrancevariants and gene-environment interaction. However, these approaches do not substitute forthe design <strong>of</strong> novel, sufficiently powered studies that apply uniform criteria to case selection,the acquisition <strong>of</strong> environmental exposure information, and to biological sample collection[354].Hereditary pancreatic cancer comprises about 10 percent <strong>of</strong> pancreatic cancer cases.Multiple causative mutations have been identified. It was described a pancreatitis/pancreaticcancer family, which demonstrates pancreatitis and pancreatic cancer resulting from anuncharacterized mutation. Family members completed evaluations to determine signs <strong>of</strong>mutation status. Select patients were screened for mutations associated with hereditarypancreatic diseases. In generation II, 12 siblings exhibit 6 cases <strong>of</strong> pancreatitis, 3 pancreaticcancer, and 2 obligate carrier status. The average age at pancreatitis diagnosis <strong>of</strong> enrolledmembers is 33 years; average age at pancreatic cancer diagnosis is 59 years. There is noassociation with known cancer syndromes. Those affected generally present with mildepigastric pain, and CT scans demonstrate characteristic fatty infiltration <strong>of</strong> the pancreaticbody and tail with sparing <strong>of</strong> the head and neck. Full sequence analysis <strong>of</strong> genes associatedwith hereditary pancreatic disease failed to demonstrate known mutations or polymorphisms.Based upon pedigree evaluation and preliminary DNA analysis, it was believed that thefamily members with pancreatitis/pancreatic cancer carry a novel genetic mutation resultingin hereditary pancreatitis. This mutation is autosomal dominant, expressed with highpenetrance, and is part <strong>of</strong> a unique hereditary syndrome that significantly increasespancreatic cancer risk [355].ScreeningSeveral masses and premalignant lesions have been detected, but the detection <strong>of</strong> the firstpancreatic cancer through an organised study <strong>of</strong> screening has yet to be published. Therehas been progress in risk stratification. A mutation in the palladin gene was found tosegregate with the disease in a family with a clear predisposition for pancreatic cancer,though this has yet to be found in other such kindreds. This means that significant challenges