Cystic fibrosis transmembrane regulator (CFTR) DeltaF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. PANKRAS II Study Group.

BACKGROUND: An increased risk of chronic pancreatitis has been described among carriers of the cystic fibrosis transmembrane regulator (CFTR) mutation. In addition, patients with cystic fibrosis may have a higher risk of exocrine pancreatic cancer. AIMS: To determine the prevalence of the DeltaF508 mutation and 5T allele, the most common CFTR disease related variants, and to assess their association with lifestyle factors in an unselected series of patients with chronic pancreatitis or pancreatic cancer. SUBJECTS: Patients recruited to the multicentre PANKRAS II study with a diagnosis of chronic pancreatitis and pancreatic cancer from whom normal DNA was available. METHODS: The DeltaF508 mutation and 5T allele were analysed using polymerase chain reaction amplified normal DNA. Information on clinical and lifestyle factors was obtained through personal interviews. RESULTS: Among patients with pancreatitis, no DeltaF508 alleles were found and the prevalence of the 5T allele was 10.5%, similar to that described in the general population. Among patients with pancreatic cancer, the prevalence of the DeltaF508 mutation and the 5T allele was 2.4% and 5.5%, respectively. 5T allele carriers with cancer consumed significantly less alcohol than non-carriers (p=0.038). CONCLUSIONS: Our findings do not support the view that the DeltaF508 mutation and 5T allele confer a higher risk of chronic pancreatitis or pancreatic cancer. Nevertheless, our data suggest that interactions between CFTR polymorphism and environmental factors may play a role in the pathogenesis of these diseases. Our study emphasises the need for a multinational study to conclusively establish the role of CFTR variants as genetic susceptibility factors for chronic pancreatitis and pancreatic cancer.

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

STUDY OBJECTIVE: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer. DESIGN: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

[Agreement between information supplied by the patient and a family member on medical history, consumption of tobacco, alcohol and coffee and diet in cancer of the exocrine pancreas and extrahepatic biliary tract]. / Concordancia entre la información facilitada por el paciente y un familiar sobre antecedentes patológicos, consumo de tabaco, de alcohol, de café, y dieta en el cáncer de páncreas exocrino y del sistema biliar extrahepático.

OBJECTIVE: No study on mutations in the K-ras oncogene and cancer of the exocrine pancreas or cancer of the biliary system has analyzed the reliability of clinical and epidemiological information. METHODS: Agreement between patient and surrogate on factors potentially related to both tumours was evaluated within a multicentre prospective study. Interviews were personally administered to both patient and surrogate (N = 110 pairs). Agreement was examined via the simple kappa index (k), the weighted kappa index (kw), the percentage of simple agreement, and the percentages of positive and negative agreement. RESULTS: Agreement for medical history was excellent (k between 0.89 and 0.76), as it was for tobacco consumption (k = 0.98). Agreement was moderate for coffee consumption (k = 0.68), frequencies of food groups (kw from 0.66 to 0.38), and consumption of alcoholic drinks (k from 0.66 to 0.32). Surrogates indicated a higher consumption of alcohol than patients. CONCLUSION: Surrogates can be an alternative source of information when patients cannot be interviewed, but information on alcohol consumption should be treated with caution.