**6. Translational outlook for environmentally-induced cancer**

As the molecular mechanisms of environmentally-induced carcinogenesis continue to emerge, a need to characterize the clinical utility of these findings should be underscored. This need is further emphasized by the complex interplay between the numerous features of the lung exposome. Many of the single cancer-associated genes that are affected by exposure to these environmental agents are promising therapeutic intervention points. For instance, targeted inhibitors of EGFR (e.g., erlotinib, afatinib)—a protein transcribed from a gene commonly up-regulated upon exposure to arsenic—are used in lung cancer treatment to interfere with the aberrant growth pathways activated by the upregulation of this signaling receptor [130]. Additionally, the association between radon exposure and *ALK* gene rearrangements in lung cancer patients may be amenable to therapy with inhibitors of the ALK protein (e.g., crizotinib, ceritinib) [131]. However, patients that do not present with alterations in genes that are clinically actionable remain extremely difficult to treat beyond standard regimes. Thus, it is critical to analyze the oncogenetic alterations induced by environmental carcinogens, to not only identify the contribution of each of these widely-distributed agents to tumorigenesis, but also to direct the development of novel treatment and risk-management strategies. Concurrent analysis of altered genes, transcripts, and proteins may help to parse out the risk associated with the varying molecular aberrations that have been observed to be induced by these compounds [132]. This approach, while difficult in terms of scale, necessitates the use of geographic, demographic, and exposome level data, which can be scarce in areas where environmental carcinogen levels are especially concerning. **Table 1** summarizes the currently available sources of information for carcinogens found in the environment that are associated with lung cancer. Overall, future mitigation of the environmental risk factors that lead to lung cancer will rely on the integration of information from the genomic to epidemiological levels.


**Table 1.**

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Research.

**Conflict of interest**

Authors declare no conflict of interest.

*Oncogenetics of Lung Cancer Induced by Environmental Carcinogens*

The geographical conditions facilitating human exposure to environmental lung carcinogens such as arsenic, asbestos and radon occur commonly across the globe. While millions of individuals are known to be exposed to potentially damaging doses of these carcinogens, another significant part of the population is unaware of its exposure. Despite the worldwide impact of the public health risk posed by these compounds, the genomic and epigenetic consequences of these exposures are drastically understudied. Barriers such as: (i) availability of individual-level exposure data; (ii) collection of genomic, epigenomic, and transcriptomic readouts following acute and chronic exposure to carcinogens; and (iii) obtaining enough samples to reach statistical power; impose even further challenges to determining the true extent of environmentally-induced

Understanding these mechanisms could have a significant impact on the estab

lishment of safe exposure limits for each of these agents. For instance, most of the current frameworks used to regulate arsenic exposure in drinking water have been derived from studies performed in specific populations exposed to high levels of arsenic, such as Bangladesh, Chile, and China [9, 133, 134]. However, an increased risk of arsenic-related health effects (including cancer) has been documented at levels below current safety thresholds that are commonly found in water sources throughout North America and Europe [7]. Thus, characterizing the effects of these agents at the genomic/epigenomic level will not only aid in determining the oncogenes that are perturbed in environmentally-induced lung cancers, but may also uncover early molecular events that can be used as diagnostic and prognostic

The fraction of lung cancer patients who have never smoked or have ceased smoking is likely to increase in the coming years. Exposure to environmental car

cinogens, such as arsenic, asbestos, and radon will play a key role in their etiology. Further elucidation of the detailed mechanisms driving environmentally-induced lung tumors will provide the much-needed insight to define specific detection meth

ods and intervention strategies. Collectively, uncovering these carcinogen-specific mechanisms, as well as the affected genes driving malignant transformation, will greatly contribute to the development of personalized approaches to provide better

This work was supported by grants from the Canadian Institutes for Health Research (CIHR FDN-143345). VDM, APS, and EAM are supported by scholar

ships from the University of British Columbia. APS is further supported by the Frederick Banting and Charles Best Scholarship from CIHR. EAM is also supported by the Vanier Canada Graduate Scholarship from CIHR. AAG is the Canada Research Chair for Radiation Exposure Disease and this work was undertaken, in part, thanks to funding from the Canada Research Chairs pro

gram. The AAG laboratory is supported by the Canadian Institutes of Health






*DOI: http://dx.doi.org/10.5772/intechopen.81064*

**7. Conclusions and future directions**

health effects.

markers.

support to lung cancer patients.

**Acknowledgements**

*Sources of information on environmental carcinogens associated with lung cancer.*

*Oncogenes and Carcinogenesis*

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