Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer

Study objective-To analyse the relation between coffee consumption and muta tions in the K-ras gene in exocrine pancreatic cancer. Design-Case-case study. Consumption of coffee among cases with the activati ng mutation in the K-ras gene was compared with that of cases without the m utation. Setting and patients-All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Stud y (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 mutati ons 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 nonr egular coffee drinkers (82.0% v 55.6%, p=0.018, n=107). The odds ratio adju sted 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 drinki ng was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/w eek and 9.99 for drinkers of greater than or equal to 15 cups/week (p<0.01, test for trend). Conclusions-Pancreatic cancer cases without activating mutations in the K-r as gene had drank significantly less coffee than cases with a mutation, wit h a significant dose response relation: the less they drank, the less likel y their tumours were to harbour a mutation. In exocrine pancreatic cancer t he K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other fac tors with which coffee drinking is associated may modulate K-ras activation .