Sex differences in lung cancer susceptibility: a review.
ABSTRACT 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.
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.
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.
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.
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.
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ABSTRACT: Worldwide lung cancer incidence is decreasing or leveling off among men, but rising among women. Sex differences in associations of tobacco carcinogens with lung cancer risk have been hypothesized, but the epidemiologic evidence is conflicting. We tested sex-smoking interaction in association with lung cancer risk within a population-based case-control study, the Environment and Genetics in Lung Cancer Etiology (EAGLE) Study (Lombardy, Italy, 2002-2005). Detailed lifetime smoking histories were collected by personal interview in 2,100 cases with incident lung cancer and 2,120 controls. Odds ratios and 95% confidence intervals for pack-years of cigarette smoking were estimated by logistic regression, adjusted for age, residence area, and time since quitting smoking. To assess sex-smoking interaction, we compared the slopes of odds ratios for logarithm of pack-years in a model for men and women combined. Overall, the slope for pack-years was steeper in men (odds ratio for female-smoking interaction = 0.39, 95% confidence interval: 0.24, 0.62; P < 0.0001); after restriction to ever smokers, the difference in slopes was much smaller (odds ratio for interaction = 0.63, 95% confidence interval: 0.29, 1.37; P = 0.24). Similar results were found by histological type. Results were unchanged when additional confounders were evaluated (e.g., tobacco type, inhalation depth, Fagerström-assessed nicotine dependence). These findings do not support a higher female susceptibility to tobacco-related lung cancer.American journal of epidemiology 02/2013; · 5.59 Impact Factor
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ABSTRACT: Lung cancer is still a leading cause of cancer mortality in the world. The incidence of lung cancer in developed countries started to decrease mainly due to global anti-smoking campaigns. However, the incidence of lung cancer in women has been increasing in recent decades for various reasons. Furthermore, since the screening of lung cancer is not as yet very effective, clinically applicable molecular markers for early diagnosis are much required. Lung cancer in women appears to have differences compared with that in men, in terms of histologic types and susceptibility to environmental risk factors. This suggests that female lung cancer can be derived by carcinogenic mechanisms different from those involved in male lung cancer. Among female lung cancer patients, many are non-smokers, which could be studied to identify alternative carcinogenic mechanisms independent from smoking-related ones. In this paper, we reviewed molecular susceptibility markers and genetic changes in lung cancer tissues observed in female lung cancer patients, which have been validated by various studies and will be helpful to understand the tumorigenesis of lung cancer.Cancers. 01/2011;
Article: Ligand-dependent differences in estrogen receptor beta-interacting proteins identified in lung adenocarcinoma cells corresponds to estrogenic responses.[show abstract] [hide abstract]
ABSTRACT: ABSTRACT: A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells. FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation. LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue. Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.Proteome Science 09/2011; 9(1):60. · 2.33 Impact Factor