Identification of Patients with Genetic Risk Factors of Pancreatitis: Impact on Treatment and Cancer Prevention

Abstract

Recent data suggest that genetic alterations are relevant risk factors for chronic pancreatitis. The highest risk is associated with autosomal-dominant mutations (N29I, R122H) of the cationic trypsinogen (PRSS1). Further mutations were identified in the genes of the pancreatic trypsin inhibitor (SPINK1) and in the cystic fibrosis transmembrane conductance regulator (CFTR). A remarkable finding was that both molecules were also mutated in patients suffering from alcoholic chronic pancreatitis. According to recent estimations, genetic alterations may be regarded as more severe risk factors than chronic alcohol consumption. To identify patients with mutations, a positive family history could be of help, but mutations were also found in a significant number of those with a negative family history. On the other hand, in approximately 40% of the patients with a positive family history no mutations were found up to now. The age at onset is lower in patients with genetic risk factors; however, no clear limit can be denominated above which a screening is not appropriate. Therefore, in our department genetic screening is offered to all patients with chronic pancreatitis of unclear origin. There is no specific treatment in patients with a genetically based disease. The patients with familial pancreatitis-increased rates of pancreas cancer were described but there is no agreement concerning the prophylactic strategy. Prevention of cancer by routine pancreatectomy, though performed recently, is not justified at the moment. Clinical criteria may be more appropriate to decide the timing and the extent of the operation.

Clinical and Morphological Characteristics of Sporadic Genetically Determined Pancreatitis as Compared to Idiopathic Pancreatitis: Higher Risk of Pancreatic Cancer in CFTR Variants

“…Indeed, even though the clinical characteristics showed minor differences between groups, pancreatic cancers seems to be predominantly associated with mutations in the CFTR gene rather than in PRSS1, a gene more typically related to an increased risk for pancreatic cancer [31,35]. Even though it seemed to be lower than that reported in other series, the increased incidence ratio of pancreatic cancers we observed in our study is in agreement with that reported by other groups.…”

“…Even though it seemed to be lower than that reported in other series, the increased incidence ratio of pancreatic cancers we observed in our study is in agreement with that reported by other groups. Indeed, a SIR of 67, which is more than twice as high as that observed in our work, has been reported in patients with PRSS1-associated hereditary pancreatitis [31], and a SIR of 53 has been recorded by the International Hereditary Pancreatitis Study Group [35]. The differences in the risk of cancer between our PRSS1 and CFTR cohorts seemed to be mainly related to smoking habits, male sex (more frequent in the CFTR group) and their older age during follow-up.…”

Update on Familial Pancreatic Cancer

“…Some of these patients therefore consider prophylactic total pancreatectomy 98–100. While this surgery will eliminate the patient’s very significant risk of developing pancreatic cancer, the benefit of prophylactic surgery has to be weighed against the real risks of total pancreatectomy 101.…”

“…While this surgery will eliminate the patient’s very significant risk of developing pancreatic cancer, the benefit of prophylactic surgery has to be weighed against the real risks of total pancreatectomy 101. The main complication of total pancreatectomy is brittle diabetes and although there is now increasing experience in managing diabetes after total pancreatectomy, there is an increased risk of morbidity and mortality associated with this surgery 98, 99, 101–103. Some have considered the option of islet autotransplantation, but the “cell of origin” for pancreatic cancer is not known, and the risk of autotransplanting a potential neoplastic cell remains a theoretical concern 98, 99, 101–103.…”