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**71**

**Chapter 5**

Carcinogens

*and Wan L. Lam*

**Abstract**

cancer.

**1. Introduction**

Oncogenetics of Lung Cancer

*Victor D. Martinez, Adam P. Sage, Erin A. Marshall,* 

*Miwa Suzuki, Aaron A. Goodarzi, Graham Dellaire* 

The molecular landscape of non-tobacco-induced primary lung tumors displays specific oncogenetic features. The etiology of these tumors has been largely associated with exposure to well-established environmental lung carcinogens such as radon, arsenic, and asbestos. Environmental carcinogens can induce specific genetic and epigenetic alterations in lung tissue, leading to aberrant function of lung cancer oncogenes and tumor suppressor genes. These molecular events result in the disruption of key cellular mechanisms, such as protection against oxidative stress and DNA damage-repair, which promotes tumor development and progression. This chapter provides a comprehensive discussion of the specific carcinogenic mechanisms associated with exposure to radon, arsenic, and asbestos. It also summarizes the main protein-coding and non-coding genes affected by exposure to these environmental agents, and the underlying molecular mechanisms promoting their deregulation in lung cancer. Finally, the chapter examines the anticipated challenges in personalized intervention strategies in non-tobacco-induced lung

**Keywords:** lung cancer, environmental carcinogens, radon, arsenic, asbestos

in the environment, affecting hundreds of millions of people worldwide.

Lung cancer remains the deadliest form of cancer across the globe [1]. While smoking rates have decreased in many areas, it remains to be seen if the incidence and mortality of primary lung cancer will experience a similar shift, particularly in light of the observation that close to 25% of cases arise in individuals who have never smoked [2]. As one of the most environmentally-influenced malignancies, lung tumorigenesis can result from exposure to both physical and chemical carcinogens. Exposure to the mix of compounds present in particulate matter is another well-known factor affecting the development of lung cancer [3]. However, a number of single-agent compounds in the environment have been identified as key lung carcinogens, particularly arsenic, asbestos and radioactive radon (222Rn) gas [4]. These compounds are distributed at varying, potentially-dangerous concentrations

Induced by Environmental
