A distinct mutational spectrum of p53 and K-ras genes in lung cancer of workers with silicosis.

Crystalline silica was recently classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, the direct genotoxic effect of silica in humans remains unclear. We examined the p53 and K-ras gene mutations in lung cancer in workers with silicosis (LCWS). DNA was extracted from paraffin-embedded tissues and examined by PCR-RFLP, PCR-SSCP, and DNA sequencing. The mutation frequencies of p53 gene were high, but the mutation distributions in exons and among the histological types of LCWS differed from those of common (i.e., not silicosis-related) lung cancer. Furthermore, no mutations in codon 12 of K-ras gene (predominant in common lung cancer) were found in LCWS. These findings in the mutational spectrum support a carcinogenic effect of silica dust at the DNA molecular level.