Occupational exposure to organic solvents and K-ras mutations in exocrine pancreatic cancer

Carcinogenesis. 2002 Jan;23(1):101-6. doi: 10.1093/carcin/23.1.101.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA, Neoplasm / genetics
  • Female
  • Genes, ras / genetics*
  • Humans
  • Interviews as Topic
  • Male
  • Middle Aged
  • Mutagenesis / drug effects
  • Mutagenesis / genetics
  • Mutation / drug effects*
  • Mutation / genetics
  • Occupational Exposure / adverse effects*
  • Occupational Health
  • Organic Chemicals / adverse effects*
  • Pancreatic Neoplasms / chemically induced
  • Pancreatic Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Solvents / adverse effects*

Substances

  • DNA, Neoplasm
  • Organic Chemicals
  • Solvents