Roadmap of lung cancer Biology (Introduction)

 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

Introduction

Lung cancer ranks as the second most prevalent malignancy, with an 11.4% incidence rate [1]. 

Over 230,000 new cases were detected in the United States in 2018, leading to more fatalities than all other cancers including breast, colon, and prostate cancer combined [2].

 According to GLOBOCAN 2020 data, approximately 2.3 million new cases (11.4%) and almost 1.8 million deaths from lung cancer were recorded in 2020 [3].

 Lung cancer is uncommon before the fifth decade of life, but its incidence rises with age [3].

 In the U.S., lung cancer incidence among males continues to decline, while females showed an initial increase followed by a decline.

 It is particularly marked among younger women who have recently demonstrated higher incidence rates than males, notably for non-Hispanic Whites and Asians/Pacific Islanders [4].

 Similarly, a study by Nolen et al. reported higher rates of lung cancer in the United States in young women than men of similar age, extending to those aged 50–54 [5].

 A very recent study showed reductions in lung cancer mortality rates that have exceeded reductions in incidence, particularly among men (5.0% vs. 2.6% annually) and women (4.3% vs. 1.1% annually) [6]. 

On the other hand, the disparity in lung cancer incidence still exists among various racial and ethnic groups. 

The highest incidence rates and the slowest decline were seen in Native Americans, with various States, including Mississippi and Kentucky, continuing to experience mortality rates two to three times higher than most Western States due to historic smoking prevalence [6]. 

In addition, Cuban males show higher incidence rates among other Hispanic groups, whereas U.S.-born Black males show higher incidence rates than Caribbean-born Blacks [7].

 Among females, US-born Blacks exhibit the highest incidence rates [7]. 

Nevertheless, lung cancer is the most common cause of cancer-related death in all parts of the world [8]. 

In 2020, lung cancer was responsible for around 1.8 million deaths, accounting for 18% of all cancer deaths.

 The age-standardized mortality rate (ASMR) was 18.0 per 100,000 (25.9 in men and 11.2 in women) [9,10].

 Mortality exhibits substantial regional variation. The highest rates are seen in countries with high Human Development Index (HDI) scores, primarily from Europe and North America, while the lowest rates are noted among those mainly located in Sub-Saharan Africa [9].

In this review article, we summarize the current knowledge of lung cancer and racial disparities, focusing on various aspects, including genomics, biology, and microbial landscapes. 

We also presented divergent histopathological and molecular subtypes, epidemiology and risk factors, histopathological and molecular progression patterns, nuclear and mitochondrial genetic alterations, epigenetic alteration, immune system dysfunction, and microbiome dysbiosis associated with lung tumorigenesis.