Int J Mol Med  2001 Oct;8(4):453-9 

Molecular analysis of p53 and K-ras in lung carcinomas of coal miners.

Sarkar FH, Li Y, Vallyathan V.

Department of Pathology, Wayne State University School of Medicine, 540 E.
Canfield Avenue, Detroit, MI 48201, USA. fsarkar@med.wayne.edu

Thirty-three cases of non-small cell lung cancers (NSCLC) from the archives of
National Coal Workers' Autopsy Study were studied for mutational alterations in
p53 and K-ras using PCR-SSCP, DNA sequencing and PCR-oligonucleotide probe
hybridization techniques. Mutations of the p53 were observed in 4 smokers (19%)
and one in a never smoker (8%). Two polymorphisms in smokers were detected at
codon 213, a common site for sequence variation. Among the smokers the p53
mutations were in the heavy smokers. In never smokers there was only a single
p53 mutation and two K-ras mutations. In never smokers the frequency of K-ras
mutations was similar (17%) in smokers, but one never smoker had two K-ras
mutations. Mutations of p53 were more frequent in adenocarcinomas (27%) and they
were AT-->GC transitions. Four of 11 (36%) adenocarcinomas were found to have
K-ras codon 12 mutations, and one adenocarcinoma had two K-ras mutations. There
were two large cell undifferentiated carcinomas with p53 mutation and one with a
K-ras mutation. Two of the 16 squamous cell carcinomas were positive for p53
mutation, while no K-ras mutations were found in this group. The results of
these preliminary studies indicate a moderately different mutational spectrum of
p53 and K-ras in coal miners independent of cigarette smoking. The mutational
spectrum observed in this study of coal miners with heavy cigarette smoking
history suggest a protective effect of coal mine dust in preventing abnormal
mutations induced by chemical carcinogens in cigarette smoke or reactive oxygen
species. These limited preliminary studies provide insight into the possibility
of accurately measuring changes in etiologic markers to unravel the
uncertainties of cancer in coal miners.

PMID: 11562787 [PubMed - indexed for MEDLINE]