Current and future perspectives in lung cancer prevention

Abstract

Smoking is one of the leading causes of morbidity and mortality worldwide. Tobacco smoke contains thousands of different heterogeneous substances, dozens of them classified as carcinogenic for humans, including tobacco-specific nitrosamines (TSNAs), metals and polycyclic aromatic hydrocarbons, among others. Deleterious effects of tobacco consumption occur not only in active smokers, but also in people passively exposed to secondhand and thirdhand smoke, the latter including children (1). There are diverse disorders associated with tobacco smoking, including cardiovascular and respiratory conditions, and cancer in multiple sites and organs (e.g., urinary bladder, stomach, lung). Lung cancer is one of the most concerning disorders associated with smoking and the first cause of cancer mortality worldwide. In 2018, an estimated 1.76 million people died of lung cancer, a higher figure than the sum of the second and third top causes of cancer-specific mortality (i.e., colorectal and stomach) (2). Lung cancer shows an overall 5-year survival rate from diagnosis of around 15–20% (3), one of the lowest among all types of cancer, result of a frequent late diagnosis in advanced stages, when the prognosis is poorer, due to the commonly unspecific initial symptoms. This survival rate has remained almost invariable for years. Around 80% of the cases of lung cancer are associated with tobacco consumption (4), while the second leading cause of lung cancer incidence, radon exposure, is linked to around 3–14% of all lung cancers (5). Remarkably, there is an important combined effect between tobacco smoking and radon exposure. Tobacco smoking, and hence lung cancer, have been historically associated with the masculine gender. However, there is nowadays a worrying increase of lung cancer incidence and mortality in women in multiple countries, consequence of the incorporation of women to tobacco smoking in the last decades due to sociocultural changes. Such is the increase in lung cancer incidence in women that lung cancer mortality in this group is going to surpass breast cancer mortality in many countries, while in others this overtake has already occurred (6). Besides, in some countries, the proportion of smoking attributable mortality is now higher in women than in men. This situation was perfectly depicted by Lopez et al. back in 1994 in their well-known descriptive model of the cigarette epidemic in developed countries (7). This model is based on four stages, defined by the prevalence of tobacco consumption and the smoking-attributable mortality in men and women at the national level. The curve of the prevalence of tobacco consumption is delayed in women around 2–3 decades with respect to the curve in men. Consequently, and also associated with the pathogenesis of lung cancer, there is also a similar lag in the curve of the proportion of lung-cancer mortality attributable to tobacco consumption between men and women (8). In some countries, well into stage four, where the proportion of smoking-attributable mortality was on the rise in women during the last years and decreasing in men, the crossover of the curves of mortality has almost or actually occurred, as reflected in the updated version of the descriptive model of Lopez et al. (9).