Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer

Abstract

Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlation between hormone replacement therapy (HRT) or oral contraceptives (OCs), and increased mortality rates due to the increased incidence of malignant tumors, including lung cancer. Interestingly, two types of estrogen receptors have been detected in lung cancer cells: ERα and ERβ. The presence of ERα has been detected in tissues and non-small-cell lung carcinoma (NSCLC) cell lines. In contrast, overexpression of ERβ is a prognostic marker in NSCLC. Herein, we summarize the current knowledge on the role of estrogens in the etiopathogenesis of lung cancer, as well as biological, hormonal and genetic sex-related differences in this neoplasm.

Clinicopathological characteristics and prognosis of breast cancer patients with lung cancer: A study based on 19,807 breast cancer patients

“…There is a strong correlation between the expression of EGFR and ER, and they play an important role in the occurrence and development of LC and BC respectively [11,12]. Previous study showed that the EGFR mutation was significantly increased in female patients with LC, and the expression [13].…”

Application of two-dimensional difference gel electrophoresis to identify protein changes between center, margin, and adjacent non-tumor tissues obtained from non-small-cell lung cancer with adenocarcinoma or squamous cell carcinoma subtype

“…Similar to testosterone, estrogen actions were found to contribute to female gender-specific risks in the development of lung carcinoma [ 148 ]. The mechanism of estradiol tumorigenesis has been linked to its interaction with estrogen receptors that have been detected in lung cancer cells [ 149 ].…”

Role of sex hormones in lung cancer

“…Regarding circulating estrogen levels, the elevation of estrogen in women together with the reduction of DNA repair capabilities, cause women more vulnerable to the cancer-causing effect of tobacco. 109–112 Stabile et al. showed that estrogen signaling is involved in both the lung mesenchyme and the epithelium.…”