Sex and Gender Differences in Lung Cancer and Chronic Obstructive Lung Disease

Abstract Two highly prevalent pulmonary diseases, lung cancer and chronic obstructive lung disease (COPD), show both sex and gender differences in their presentations and outcomes. Sex differences are defined as biological differences associated with the male vs female genotype, and gender differences are defined as behavioral or social differences that primarily arise because of gender identity. The incidence of both lung cancer and COPD has increased dramatically in women over the past 50 years, and both are associated with chronic pulmonary inflammation. Development of COPD is also a risk factor for lung cancer. In this review, the main differences in lung cancer and COPD biology observed between men and women will be summarized. Potential causative factors will be discussed, including the role of estrogen in promoting pro-growth and inflammatory phenotypes which may contribute to development of both lung cancer and COPD. Response of the innate and adaptive immune system to estrogen is a likely factor in the biology of both lung cancer and COPD. Estrogen available from synthesis by reproductive organs as well as local pulmonary estrogen synthesis may be involved in activating estrogen receptors expressed by multiple cell types in the lung. Estrogenic actions, although more pronounced in women, may also have importance in the biology of lung cancer and COPD in men. Effects of estrogen are also timing and context dependent; the multiple cell types that mediate estrogen action in the lungs may confer both positive and negative effects on disease processes.