The relative influence of diet and serum concentrations of organochlorine compounds on K-ras mutations in exocrine pancreatic cancer

Chemosphere. 2010 Apr;79(7):686-97. doi: 10.1016/j.chemosphere.2010.03.011. Epub 2010 Mar 29.

Abstract

Background: In exocrine pancreatic cancer (EPC) mechanistic relationships may exist among some organochlorine compounds (OCs) and mutations in the K-ras oncogene, as well as among the latter and dietary factors.

Objective: To analyze (1) the relationship between food intake and serum concentrations of OCs in EPC patients and (2) the relative influence of food and OCs on the frequency of K-ras mutations in EPC.

Patients and methods: Incident cases of EPC were prospectively identified, and interviewed face-to-face during hospital admission (N=135 patients with data on OCs and diet, and N=97 with additional information on K-ras status). OCs were measured by high-resolution gas chromatography with electron-capture detection.

Results: Consumption of milk and other dairy products was positively associated with concentrations of p,p'-DDT, PCB 138 and PCB 153 (log-transformed betas=0.652, 0.588 and 0.317, respectively; all p<0.05). When adjusted by OCs, dairy products were no longer associated with K-ras. By contrast, after adjusting by consumption of dairy products, patients with the highest concentrations of p,p'-DDT and some PCBs remained more likely to have a K-ras-mutated EPC than patients with lower concentrations (OR for upper tertile of PCB 138=5.5, 95% CI: 1.3-23.4).

Conclusions: Dairy products were a source of OCs. The association between dairy products and K-ras mutations was not independent of OCs. By contrast, the association between OCs and K-ras was not confounded by dairy products. OCs may be more likely to contribute to the occurrence of K-ras mutations than nutrients contained in dairy products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cattle
  • Chromatography, Gas
  • Diet
  • Environmental Pollutants / blood*
  • Environmental Pollutants / chemistry
  • Female
  • Food Analysis
  • Humans
  • Hydrocarbons, Chlorinated / blood*
  • Hydrocarbons, Chlorinated / chemistry
  • Interviews as Topic
  • Male
  • Middle Aged
  • Milk / chemistry
  • Mutation
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / genetics
  • ras Proteins / genetics*

Substances

  • Environmental Pollutants
  • Hydrocarbons, Chlorinated
  • ras Proteins