Lung Cancer in Women: The Differences in Epidemiology, Biology and Treatment Outcomes

Maria Patricia Rivera

Disclosures

Expert Rev Resp Med. 2009;3(6):627-634. 

In This Article

Molecular Aberrations

Many genetic alterations of tumor suppressor genes (p53) and oncogenes (K-ras) have been reported in lung cancer. Approximately 90% of small-cell lung cancer (SCLC) and approximately 40–70% of non-small cell lung cancers (NSCLCs) are found to have alterations in the p53 gene.[17,18] Mutations in the p53 suppressor gene result in a loss of DNA repair capacity as well as inhibition of normal apoptosis. Of the Ras family of oncogenes, K-ras is the most commonly affected gene. Several studies suggest that women may be more predisposed to molecular aberrations as a result of the carcinogenic effects of tobacco smoke.

Smoking has been found to induce p53 mutations via the formation of DNA adducts, and female smokers have been found to have higher levels of DNA adducts in the lung compared with male smokers.[19] Kure et al. found a higher frequency of the dominant p53 mutation (G:C to T:A transversion) and a higher average DNA adduct level in NSCLC from female smokers compared with male smokers.[20] In a study of 705 cases of lung cancer for which smoke exposure data were available, Tayooka et al. found that there was a higher frequency of p53 mutations in women smokers compared with women who had never smoked, and concluded that lung cancers in women smokers demonstrated significantly more tobacco-related mutations than in women nonsmokers and male smokers.[21]

The K-ras oncogene encodes a protein that is known to be oncogenic when mutated or overexpressed. As is seen with the p53 gene mutation, the formation of DNA adducts secondary to the effects of smoking appears to be linked with the K-ras oncogene.[22] Mutations in the K-ras oncogene have been reported to occur predominantly in adenocarcinomas, only in patients who have a history of smoking, and are more common in women than in men (26.2 and 17.4%, respectively).[23,24]

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