Occupational exposure to
hydrocarbon solvents has been found to be associated with an increased risk of exocrine
pancreatic cancer (
EPC), the human
tumor with the highest prevalence of K-ras mutations. Ras genes are critical
DNA targets for chemical
carcinogens. We analysed the relationship between past occupational exposure to
hydrocarbon solvents and mutations in
codon 12 of the K-ras gene in 107 incident cases of
EPC. Information on occupational factors and life-style was obtained from personal interviews conducted during
hospital stay. Occupational exposure to
hydrocarbon solvents (aliphatic, aromatic, chlorinated,
benzene, other organic
solvents) was examined using two methods: expert assessment and the Finnish job-exposure matrix (Finjem). Exposure among K-ras mutated
EPC cases (n = 83) was compared with that of K-ras wild-type
EPC cases (n = 24). An association between K-ras mutations and
solvent exposure was observed with Finjem but barely so with the expert assessment. Over 7-fold increased odds ratios (OR) were found for every group of
solvents evaluated with Finjem (all P < 0.05). On the basis of the expert assessment, K-ras mutations were significantly associated only with exposure to
benzene in men (OR = 7.07, P < 0.05). When requiring exposure to have occurred according to both the experts and Finjem, over 4-fold risks were obtained for aromatic, aliphatic, and for "any
hydrocarbon solvent". A significantly higher proportion of cases with a mutation from
glycine to
valine (GGT-->GTT) or to
aspartic acid (GGT-->
GAT) were exposed to a
hydrocarbon solvent. The results raise the possibility that
hydrocarbon solvents might be involved in the pathogenesis of
EPC, possibly through indirect modulation of K-ras activation. Since this is only the first study on occupational exposures and K-ras mutations in
EPC, studies able to refute or to confirm the findings are required before public health implications, if any, are assessed.