Lung tumor KRAS and TP53 mutations in nonsmokers reflect exposure to PAH-rich coal combustion emissions.
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.
DeMarini
D M
DM
Environmental Carcinogenesis Division (MD-68), United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. demarini.david@epa.gov
Landi
S
S
Tian
D
D
Hanley
N M
NM
Li
X
X
Hu
F
F
Roop
B C
BC
Mass
M J
MJ
Keohavong
P
P
Gao
W
W
Olivier
M
M
Hainaut
P
P
Mumford
J L
JL
D016902:Air Pollution, Indoor / Q000009:adverse effects; D003031:Coal / Q000009:adverse effects*; D004781:Environmental Exposure; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D003031:Coal; D011084:Polycyclic Aromatic Hydrocarbons; D012906:Smoke