Lung Cancer and Risk Factors

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International Journal of Molecular Sciences logo

Int J Mol Sci. 2025 Apr 17;26(8):3818. doi: 10.3390/ijms26083818

The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity

Enas S Alsatari 1,2, Kelly R Smith 1,2, Sapthala P Loku Galappaththi 1,2, Elba A Turbat-Herrera 1,2, Santanu Dasgupta 1,2,3,*

Editor: Robert Arthur  Kratzke

2.2. Environmental and Lifestyle Risk Factors

Epidemiology and risk factors involve a complex interaction of environmental, genetic mutations, and lifestyle factors that contribute to susceptibility to lung cancer and its outcomes [16,17].

 However, these interactions become more significant when considering ethnic and ancestor differences. 

Although smoking is the predominant cause of lung cancer, another study revealed that 10–25% of all lung cancer patients have never smoked [18].

 This disparity underscores the need to investigate additional risk factors other than smoking, especially in populations where lung cancer is not related to smoking [19].

 Cigarette smoking remains a major risk factor for lung cancer development. The initiation of smoking habits is mediated by peer pressure, family habits, and psychological distress [20,21]. 

Interestingly, Harrell et al. reported that demographic factors such as race, socioeconomic status, and pubertal development were significant predictors of early smoking initiation among schoolchildren [22].

 Additionally, preventative measures for air pollution include techniques like urea-selective catalytic reduction (SCR), diesel particulate filters, and NOx storage-reduction catalysts approved to enhance air quality to avoid additional health effects from gaseous as well as particulate air pollution pollutants [23].

 As a reason, there were substantial declines in lung cancer incidence in the USA from 2007 to 2018. On the other hand, there has been little change in rates among never-smokers, though rates increased significantly in Asian and Pacific Islander populations [24].

 In Denmark, lung cancer trends are influenced by historical smoking patterns, where a decline in male smoking rates led to reduced incidence. In contrast, the prevalence of smoking in women remained stable for longer, contributing to a later increase in lung cancer incidence [25].

 Existing evidence suggests that passive smoke is the cause of a significant proportion of lung cancer in women.

 For instance, Du et al. reported that passive smoking accounts for about 17.9% of lung cancer cases among never-smoking women, most of them exposed to household smoking [26]

. Moreover, a study of Moroccan women showed that 75% of lung cancer cases were recorded in never-smokers, and LUAD was the most common subtype among passive smokers [27].

Zhu et al. reported that non-smoking people who drink tea ≥ 2 cups/day have a greater risk of lung cancer [28]. 

At the population level, cigarette smoking is the primary determinant of the occurrence of lung cancer [29].

 Environmental factors increase the risk of developing lung cancer, such as air pollution, occupational exposure, secondhand smoke, and radiation exposure [30,31].

 In China, a study by Liu et al. observed that occupational environment and meteorological conditions synergistically affect lung cancer development [32]. 

Furthermore, Chinese-style cooking increases lung cancer risk [33].

 Moreover, long-term exposure to air pollutants such as PM2.5, NO2, and NOx significantly increases the risk of developing lung cancer [34]. The World Cancer Research Fund (WCRF) reported that drinking water with high concentrations of arsenic increases lung cancer risk, and the evidence was reported as “convincing” [35]. Additional interaction of these air pollutants with poor lifestyle and high genetic risk dramatically raises the likelihood of lung cancer occurrence [35]. Similarly, Huang et al. showed the same results [36]. However, predicting cancer associated with environmental factors like alcohol consumption and smoking can alter based on the variation in polymorphism of xenobiotic metabolizing enzymes (XME) genes [37]. Pettit et al. studied the genetic correlation between various traits and lung cancer risk, indicating a negative genetic correlation between lung cancer risk and some traits, including dietary behaviors, fitness metrics, educational attainment, and other psychosocial characteristics. On the contrary, the body mass index (BMI) showed a positive genetic correlation with the likelihood of lung cancer [38].

The relationship between lung cancer risk and dietary items like fruits, vegetables, micronutrients, phytochemicals, fat, and beverages has been studied. An increased intake of fruits, vegetables, and carotenoid-rich foods is associated with a reduced risk of developing lung cancer [35].

On the contrary, higher intake of retinol, red meat intake, processed meat intake, alcohol drinking, and dietary fat have been associated with an increased risk of lung cancer. 

However, no link has been reported between the phytochemical “bioflavonoid” and lung cancer risk