KI-RAS MUTATIONS IN EXOCRINE PANCREATIC-CANCER - ASSOCIATION WITH CLINICOPATHOLOGICAL CHARACTERISTICS AND WITH TOBACCO AND ALCOHOL-CONSUMPTION

The aims of this study were (i) to assess the prevalence and spectrum of codon 12 Ki-ros mutations in patients diagnosed with exocrine pancr eatic cancer (EPC) in 2 general hospitals between 1980 and 1990, (ii) to analyze the association of this genetic alteration with clinical an d pathological characteristics, and (iii) to determine the association of Ki-ros mutations with tobacco and alcohol consumption. DNA was amp lified from paraffin-embedded tissue samples and mutations in codon 12 of Ki-ros were detected using the artificial RFLP technique. Cox prop ortional-hazards regression and unconditional logistic regression were applied. Codon 12 Ki-ras mutations were detected in 30 of 51 cases fo r which molecular results were available. The amino-acid substitutions were Asp (8), Val (6), and Arg (3). A double mutation, including alwa ys a Val, was detected in 5 cases. None of the 4 nonductal pancreatic neoplasms were mutated. The mutation prevalence was 79% in metastases and 54% in primary tumors. The risk of a mutated tumor was 3 times hig her in alcohol drinkers than in non-drinkers, and a linear trend was a pparent. When age, gender, hospital, and tobacco and alcohol consumpti on were taken into account, a high risk for mutations was detected in patients who only smoked and in patients who only drank, but less so i n patients who both smoked and drank. These results raise novel hypoth eses regarding the role of tobacco and alcohol in EPC. (C) 1997 Wiley- Liss, Inc.