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

Our plain-English summary of Occupational exposure to dyes, metals, polycyclic aromatic hydrocarbons and other agents and K-ras activation in human exocrine pancreatic cancer, by J. Alguacil, M. Porta, T. Kauppinen, et al (International Journal of Cancer, 2003).

The study

• Authors: J. Alguacil, M. Porta, T. Kauppinen, N. Malats, M. Kogevinas, A. Carrato, PANKRAS II Study Group
• Journal: International Journal of Cancer
• Published: 2003;107(4):635-41
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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 (Finjem). Specific occupational exposures among K-ras mutated EPC cases (n = 83) were compared to those of K-ras wild-type 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.

Copyright 2003 Wiley-Liss, Inc.

In plain English

This Spanish study asked whether workplace exposures were linked to K-ras gene mutations in exocrine pancreatic cancer tumors. Of 185 patients at 5 eastern Spanish hospitals (1992 to 1995), 107 had gene and job data: 83 with the mutation, 24 without. Exposures from hospital interviews were rated by industrial hygienists and a Finnish job-exposure matrix. Comparing all mutated with non-mutated cases, the only statistically significant increase was for hygienist-rated dyes and organic pigments: 7 of 83 mutated and 0 of 24 non-mutated cases exposed (odds ratio 4.8, 95% confidence interval 1.02 to unquantifiably high). Limited to glycine-to-valine mutations, hygienist-rated lead also had a raised odds ratio, with a confidence interval from 1.25 to unquantifiably high. Raised, non-significant odds ratios for lead, polycyclic aromatic hydrocarbons, nickel and inhaled chromium varied by assessment method; hygienists found no increase for polycyclic aromatic hydrocarbons. Hygienist-rated skin or inhaled chromium exposure was less common in mutated cases (odds ratio 0.15, 0.03 to 0.76). Noting the small numbers, the authors concluded that results lend moderate support to an indirect link between dyes and organic pigments and K-ras activation.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case-case comparison within a hospital-based series of incident pancreatic cancer cases: patients whose tumors had a K-ras mutation were compared with patients whose tumors did not, using multivariate-adjusted odds ratios from unconditional logistic regression
• Who was studied: 107 patients with incident exocrine pancreatic cancer (EPC) with known K-ras status and occupational data, drawn from 185 cases identified in 1992 to 1995 at 5 general hospitals in eastern Spain; 83 had a K-ras mutation and 24 did not
• Exposure: Past occupational exposures assessed from hospital interviews. Two industrial hygienists rated 22 suspected carcinogens. The Finnish job-exposure matrix (Finjem) covered 21 chemical agents and 2 physical exposures. Agents included dyes and organic pigments, lead, chromium, nickel, polycyclic aromatic hydrocarbons, pesticides, gasoline, engine exhaust and sedentary work.
• Main results:
  • Dyes and organic pigments (industrial hygienist assessment): 7 of 83 K-ras mutated cases (8.4%) exposed versus 0 of 24 wild-type cases. Odds ratio 4.8, 95% CI 1.02 to unquantifiably high. This was the only statistically significant difference among exposures assessed only by the hygienists, in the comparison of all mutated with all wild-type cases.
  • Lead (industrial hygienist assessment): 7 mutated cases (8.4%) exposed versus 0 wild-type cases. Odds ratio 4.8 (95% CI 0.67 to unquantifiably high), not statistically significant.
  • Mutation-type analysis (Table IV): when cases with a glycine-to-valine mutation (21 cases) were compared with wild-type cases, hygienist-assessed lead exposure had a raised odds ratio whose 95% CI ran from 1.25 to unquantifiably high. For inhaled chromium by Finjem the odds ratio was 9.88 (95% CI 0.48 to 424).
  • Polycyclic aromatic hydrocarbons: the Finjem assessment gave an odds ratio of 4.8 (95% CI 0.61 to unquantifiably high), with 7 mutated and 0 wild-type cases exposed. The industrial hygienist assessment showed no increase (odds ratio 0.91, 95% CI 0.17 to 7.01).
  • Inhaled chromium compounds (Finjem): 8 mutated cases (9.6%) versus 1 wild-type case (4.2%). Odds ratio 3.47 (95% CI 0.50 to 71.6). Dermal and inhalatory chromium exposure rated by the hygienists was less frequent in mutated cases: 3 (3.6%) versus 5 (20.8%), odds ratio 0.15 (95% CI 0.03 to 0.76).
  • Agents assessed only with Finjem, such as gasoline engine exhaust and sedentary work, showed increased odds ratios, but none was statistically significant.
• The authors' conclusion: The authors concluded that the results lend moderate support to the hypothesis of indirect relationships between occupational exposure to dyes and organic pigments and activation of the K-ras gene in exocrine pancreatic cancer. They added that special caution is needed in interpreting the results because this is the first such study.
• Limitations the authors state:
  • The number of subjects was small and most results were not statistically significant
  • Several estimates were imprecise and some associations might have emerged by chance
  • Several hundred cases would likely be needed for precise estimates of associations with specific mutation types
  • Special caution is needed when using mutation spectra to judge the role of occupational exposures
  • As the first study of these exposures and K-ras mutations in this cancer, the results need cautious interpretation

Topics

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Odds Ratio.

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