K- ras mutations in lung carcinomas from nonsmoking women exposed to unvented coal smoke in China

Abstract

Lung cancer mortality rate in nonsmoking women in Xuan Wei (XW) County is the highest in China. The XW lung cancer rate is associated with exposure to coal smoke, containing high concentrations of polycyclic aromatic hydrocarbons (PAHs), in unvented homes. Here we investigated codon 12 K- ras mutations in lung tumors or sputum samples from 102 XW lung cancer patients (41 nonsmoking women and 61 smoking men). In addition, we analyzed specimens from 50 lung cancer patients (14 nonsmoking women, 33 smoking men and three nonsmoking men), from Beijing and Henan (B&H), where natural gas is the main domestic fuel. K- ras mutations were found in nine women (21.9%) and 14 men (22.9%) from XW, with G to T transversions accounting for 66.7 and 85.7%, respectively. Among B&H patients, one woman (7.1%) and six men (16.7%) had K- ras mutations, with G to T transversions accounting for 66.7% of the mutations in the men. Therefore, the frequency and type of K- ras mutations in XW nonsmoking women are similar to those of K- ras mutations found in both XW and B&H smoking men. On the other hand, the mutation frequency in XW women is higher than, although not statistically significant from, that in the B&H nonsmoking women ( P=0.28, two-sided Fisher's Exact Test). These results suggest an association between exposure to coal smoke and the increased K- ras mutation frequency in XW nonsmoking female lung cancer patients. They also suggest that the mutagens and/or mechanisms of mutations in these nonsmoking women are similar to those responsible for K- ras mutations in cigarette smoking lung cancer patients, which are probably induced largely by chemicals such as PAHs.