Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences.

Seventy-seven pancreatic adenocarcinomas (60 Spanish and 17 Italian) were tested for Ki-ras gene mutations by analysis of polymerase chain reaction amplified sequences. Mutations involving codon 12 (GGT; gly) were detected in 16 Italian and 46 Spanish cases (80.5% in total). All Italian mutations involved the second base and were G to A transitions (GAT; asp) in 8 cases and G to T transversions (GTT; val) in the remaining 8. Forty-two Spanish mutations were characterized. Thirty-eight were at the second and 4 at the first base: asp in 24 cancers, val in 14, arg (CGT) in 2 and cys (TGT) in 2. Previous European studies and our present data show that 149 of the 186 pancreatic cancers harbored a codon 12 Ki-ras mutation (80%), the large majority affecting the second base (73%), with a transitions/transversions ratio of 1.3:1. However, the mutational pattern of cancers of the different European countries shows remarkable differences, both in the site of the mutation (first or second base) and in the ratio of transitions over transversions. Moreover, a significant subgroup of pancreatic carcinomas do not harbor Ki-ras mutations. The classification of pancreatic cancers, according to the presence or absence, and type of Ki-ras mutation, may be of importance in epidemiological studies. A critical reappraisal of existing epidemiological data, through a retrospective genotypic study using paraffin-embedded cancer samples, may reveal significant correlations with specific genotoxic agents.