Sex Differences in Lung Cancer Susceptibility: A Review

Background: Several epidemiologic and molecular epidemiologic studies have indicated that, for a given number of cigarettes smoked, women may be at higher risk of lung cancer compared with men. Objective: The objective of this article was to address sex differences in lung cancer susceptibility, with special emphasis on genetic, biological, and sex-related hormonal factors. Methods: Using the search terms gender or sex difference in combination with lung cancer, susceptibility, survival, polymorphism, biomarker, and smoking, we conducted a review of the available literature in the MEDLINE, Current Contents, and Web of Science biomedical databases. Relevant English-language publications (January 1966-December 2009) on sex differences in lung cancer were identified. Results: Higher levels of polycyclic aromatic hydrocarbon DNA adducts were observed in female lung cancer patients compared with their male counterparts, even though the level of tobacco carcinogens was lower among women than among men. DNA repair capacity was found to be lower in female lung cancer patients than in their male counterparts. A higher frequency of G-to-T transversion mutations in the tumor suppressor protein p53 gene has been observed in women compared with men. Non-small cell lung tumors in women appeared to be more likely than those in men to harbor K-ras, c-erbB-2, or epidermal growth factor receptor mutations. Sex differences have been identified in the expression of the cytochrome P4501A1 gene and gastrin-releasing peptide receptor gene, with women exhibiting higher gene expression than men for both of these genes. Evidence supporting a possible association between estrogen and lung cancer risk based on epidemiologic studies has not been consistent, but sex hormones may influence susceptibility to lung carcinogenesis. Conclusions: Women may be more susceptible to tobacco smoke and potentially more vulnerable to lung cancer development. If additional studies yield supporting evidence, researchers, the public, and policy makers should focus on ways to reduce the risk of lung cancer for women. (Gend Med. 2010;7:381-401) (C) 2010 Excerpta Medica Inc.