Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions

Cancer Res. 2001 Sep 15;61(18):6679-81.

Abstract

We determined the TP53 and codon 12 KRAS mutations in lung tumors from 24 nonsmokers whose tumors were associated with exposure to smoky coal. Among any tumors studied previously, these showed the highest percentage of mutations that (a) were G --> T transversions at either KRAS (86%) or TP53 (76%), (b) clustered at the G-rich codons 153-158 of TP53 (33%), and (c) had 100% of the guanines of the G --> T transversions on the nontranscribed strand. This mutation spectrum is consistent with an exposure to polycyclic aromatic hydrocarbons, which are the primary component of the smoky coal emissions. These results show that mutations in the TP53 and KRAS genes can reflect a specific environmental exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Pollution, Indoor / adverse effects
  • Coal / adverse effects*
  • Environmental Exposure
  • Female
  • Genes, p53 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Middle Aged
  • Mutation*
  • Polycyclic Aromatic Hydrocarbons / adverse effects*
  • Smoke / adverse effects
  • Smoking / adverse effects
  • Smoking / genetics

Substances

  • Coal
  • Polycyclic Aromatic Hydrocarbons
  • Smoke