Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K-ras activation in human exocrine pancreatic cancer

ras genes are known critical DNA targets for chemical carcinogens. Exocrine pancreatic cancer (EPC) is the human tumor with the highest prevalence of K-ras mutations at diagnosis. We analyzed the relationship between past occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons (PAHs) and other agents and mutations in codon 12 of the K-ras gene in 107 incident cases of EPC. Information on occupational and life-style factors was obtained from personal interviews conducted during hospital stay. Occupational exposures were examined using industrial hygienists (IH) assessment and the Finnish job-exposure matrix (Fin-jem). Specific occupational exposures among K-ras mutated EPC cases (n = 83) were compared to those of K-ras wildtype EPC cases (n = 24) (case-case analysis). Multivariate-adjusted odds ratios (OR) and their corresponding 95% confidence limits were estimated by unconditional logistic regression. Cases with K-ras mutations were significantly more likely than wild-type cases to have been exposed to dyes and organic pigments (OR 4.8;p<0.05). There was some indication of weaker associations between K-ras mutations and occupational exposure to lead, PAHs, benzo[a]pyrene, gasoline, nickel, inhalatory exposure to chromium and sedentary work. The association with chromium compounds was stronger for G to T transversions, a finding compatible with experimental studies on mutation spectra for chromium. Results lend moderate support to the hypothesis of indirect relationships between occupational exposure to dyes and organic pigments and the activation of the K-ras gene in the etiopathogenesis of human exocrine pancreatic cancer. (C) 2003 Wiley-Liss, Inc.