Epidemiological trends of tracheal, bronchus, and lung cancer at the global, regional, and national levels: a population-based study

Lung cancer was uncommon before the twentieth century, but it ranks the second and is the leading cause of cancer mortality. In addition, various factors play a crucial role in the occurrence, infiltration, metastasis of tracheal, bronchus, and lung (TBL) cancer, such as environmental and genetic factors [1, 2]. In recent years, substantial progress has been attained in terms of early diagnosis of and therapy options for TBL cancer [3]. However, the TBL cancer burden is still increasing owing to the aging population and risk factors such as pollution, dietary habits, and tobacco, which vary among different countries [4‐6]. Further knowledge about TBL cancer burden is necessary to better allocate the limited health resources worldwide, which is helpful for the prevention, diagnosis, and treatment of TBL cancer.

The Global Burden of Disease (GBD) study included 354 diseases and injuries in 195 countries and territories worldwide, providing an opportunity to perform comprehensive assessments of disease incidence, mortality, disability-adjusted life years (DALY), and change trends of TBL cancer [7]. To better understand the TBL cancer burden among geographical locations, the social development index (SDI), age groups, and sexes, we conducted various subgroup analyses to assess the burden and variation trends of TBL cancer on the basis of data from the GBD study 2017.

At present, lung cancer continues to be a major global public health problem. The ASIR was stable globally, but the ASDR and age-standardized DALY rate decreased generally. However, the change trend of ASIR and ASDR among sexes was on the contrary. ASIR and ASDR of TBL cancer in females showed an increasing trend, which is contrary to males. Therefore, though males carried the majority burden of TBL cancer, we should attach importance to the higher growth rate of women and its related risk factors among various regions [12]. The burden of lung cancer in men was reported largely determined by smoking patterns, although other factors such as air pollution and occupational exposure also play a role. While the burden of lung cancer in women was found to be associated primarily with smoking patterns, it is also associated with other risk factors, including air pollution and occupational exposure et al. [13]. Especially in East Asia, where smoking by women remained uncommon, indoor air pollution from cooking and heating played a major role in lung cancer incidence [14]. Age-standardized DALY rate of TBL cancer kept decreasing in both genders worldwide, which might due to the improvement of lung cancer treatment [15, 16] and variation of related risk factors, which was consistent with the global disease trend [17].

The burden and its trend of TBL cancer varied among regions. East Asia, Western Europe, and high-income North America (Canada and USA), where smoking uptake began earliest, had higher burden of TBL cancer, which might result from historical smoking patterns [18] and epidemic [12]. Indeed, lung cancer mortality began to increase 20 to 30 years after the onset of widespread smoking, and peak 30 to 40 years after the peak of smoking in the population [19]. Burdens were imbalanced among the five SDI quintiles, which might result from the inequalities in access to health care [20‐22]. At present, one third of the TBL cancer burden was in the high SDI quintile, where ASRs decreased most, which might benefit from the advanced medical conditions [23, 24]. A previous study in California showed that in the high SDI quintile, the TBL burden among males decreased [25]. All indicators were always lowest in the low SDI quintile. However, data in low SDI quintile is scarce, and the detected trends should be treated cautiously.

China and the USA always had the highest burden of TBL cancer, which might be partly due to their high population. Females in the UK and males in Russia also bore a great TBL cancer burden. It is reported that the mortality of lung cancer declined in the USA, benefiting from the decline in smoking rates and clean air legislation [26]. In 2017, Greenland and Hungary had higher ASRs than other districts, whereas Malawi had the lowest. Consistent with the previous data, the ASIR and ASDR of lung cancer in Hungary were higher than those in Western-European countries [27]. Another study also stated that the incidence and survival rates of lung cancer in Greenland were comparable to those in northern European countries [28]. In addition, females in Spain and France, and males in Georgia and China had a faster increase of ASRs, which deserves further investigation. In Europe, lung cancer rates were falling for smoking men and rising for smoking women overtime [29]. Previous studies indicated that female heavy smokers had a higher risk of lung cancer compared to men [30, 31]. The gender difference may stem from differences in the number of men and women who smoke and how their bodies react to tobacco. In addition to smoking and other sex-related factors that may increase a woman’s susceptibility to lung cancer, such as genetic susceptibility, sex hormone exposure [32, 33], and molecular characteristics [34]. However, the biological basis of gender differences is controversial and requires further evaluation.

ASRs were also higher in Australasia [35], Europe, and East Asia. South Asia, Western, and Eastern sub-Saharan Africa had the lowest ASRs. The huge differences in TBL cancer morbidity and mortality among sexes, countries, and regions remind us that the government should investigate in-depth the reasons such as genetic factors, risk factors, policy adoption, and medical technology. A previous study described that the difference in lung cancer mortality between genders in Latin America was attributable to smoking patterns [36]. The burden of lung cancer varied in different countries and regions partially result from the gap of health-care resources [37‐39], leading to different opportunities for diagnosis and treatment outcomes.

The leading cause of death and DALYs was behavioral risks (including smoking, secondhand smoke, and low-fruit diet), followed by environmental/occupational and metabolic risks (high-fasting plasma glucose level). The contribution of all the risk factors to death increased with age, which showed an accumulative effect [40]. In high-income North America and Asia, the government should take necessary measures to alter the impact of behavioral risks on ASDR. The mortality rates of lung cancer were high in countries where smoking uptake began earliest, especially in North America and Europe [41]. In the low-middle and low SDI quintiles, the top 3 risk factors of TBL cancer deaths and DALYs were air pollution, tobacco, and dietary risks (low-fruit diet). In China, high levels of fine particulate matter (PM2.5) might attribute to its huge TBL cancer burden [26, 42]. Measures to prevent and control home ambient particulate matter pollution and household air pollution from solid fuels should be further strengthened [43], especially in less developed areas. ASRs attributable to tobacco among females increased until 2013 and then decreased, which might have resulted from the period of smoking cessation. Women started quitting smoking mostly in the 1980s, which was later than the anti-smoking movement by the US Department of Health in 1964 [12]. For males, the effect of tobacco on the prognosis of patients with TBL cancer has diminished, consistent with the previous cigarette epidemic [18]. These changes are largely due to the tobacco control worldwide. Lung cancer mortality rates began to increase in the population 20 to 30 years after widespread smoking began [12]. Although tobacco control was popular in the past 50 years, the decline in smoking rates may have stalled at the current levels.

As regards metabolic risks (high-fasting plasma glucose level), the prognosis in female patients showed an increasing trend, whereas that of males was stable. Metabolic risk-related [44] ASDR increased in most regions, indicating fasting glucose level elevated TBL cancer death. Some studies provided evidence that diabetes correlated with an elevated risk of lung cancer mortality [45, 46], and baseline fasting plasma glucose level was an independent predictor of lung cancer survival [47]. Another large prospective study revealed that pre-existing diabetes was related to the poor prognosis in women with lung cancer [48]. A meta-analysis suggested that diabetics patients have an increased risk of lung cancer, especially women [49], similar to another study [50]. The mechanisms of the difference between genders, such as hormonal and environmental levels, deserve further investigation.

The main strength of this study is that we presented a comprehensive review of the TBL cancer burden based on the most recent national estimated data worldwide. However, this study also has some limits. Owing to the breadth and complexity of the data, the TBL cancer burden should be interpreted with caution. Few data are available from countries with lower SDI values, and the burden may be underestimated owing to the different levels of registration management. Although the GBD study data are considered of high quality, the accuracy of cancer information collected, extracted, and reported in population-based cancer registries must be improved. Owing to the lack of specific information such as TBL cancer classification, staging, and treatment, further analysis is difficult to achieve.

Our study provides a comprehensive overview of the global TBL cancer burden. Incidence, mortality, DALYs, ASRs, and their trends varied substantially by gender, age, socioeconomic status, ethnicity, and geography. The incident cases, mortality, and DALYs of TBL cancer kept increasing worldwide. Asia had the greatest TBL cancer burden, followed by high-income North America. The leading cause of death and DALYs in TBL cancer was tobacco, followed by air pollution. Further investigation is warranted to determine the causes of these changes.