Lung Cancer: Genetics

Abstract

There exists sufficient evidence supporting a genetic component to lung cancer development. However, the genes involved and the exact mechanisms underlying individual susceptibility to lung cancer development are still unclear. In addition, lung tumours demonstrate a multitude of genetic alterations, of which several are known to drive lung malignancy growth and invasion. These driver alterations are currently being exploited in the development of targeted treatments, improving lung cancer therapy. Similarly, the study of the genetics of lung cancer is an ongoing field of investigation, and technological advancements are providing a better understanding of the genetic nature of the disease. Advancements are expected to improve both our understanding of lung cancer and the management of the disease in the clinical setting.

Key Concepts

  • Lung cancer is the number one cause of cancer‐related mortality.
  • Tobacco smoke exposure is linked to 85–90% of all lung cancers, although only 15% of all smokers will develop lung cancer in their life.
  • A family history of lung cancer is a strong indicator of an individual's risk of developing lung cancer, suggesting that genetics plays a role in susceptibility.
  • Family‐based linkage analyses have established a region on chromosome 6q23‐25 as containing a major lung cancer susceptibility locus in familial lung cancer.
  • Variation in the carcinogen metabolism and DNA repair pathways have been implicated as modulators of an individual's susceptibility to lung cancer, given a sufficient carcinogen exposure.
  • Genome‐wide association studies have discovered multiple loci associated with the risk of lung cancer in several distinct populations.
  • Genome and exome sequencing are useful tools to understand malignancy‐driven genetic variation within lung tumours.
  • Commonly occurring somatic mutations are the focus of ongoing clinical investigation to improve lung cancer therapies.

Keywords: lung cancer; genetics; genomics; genome‐wide association study; gene expression

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Further Reading

Cooper WA, Lam DCL, O'Toole SA and Minna JD (2013) Molecular biology of lung cancer. Journal of Thoracic Disease 5 (5): 479–490.

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Watza, Donovan, Cote, Michele L, and Schwartz, Ann G(Apr 2017) Lung Cancer: Genetics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005834.pub2]