title: Genomic impact of cigarette smoke, with application to three smoking-related diseases.
abstract: There is considerable evidence that inhaled toxicants such as cigarette smoke can cause both irreversible changes to the genetic material (DNA mutations) and putatively reversible changes to the epigenetic landscape (changes in the DNA methylation and chromatin modification state). The diseases that are believed to involve genetic and epigenetic perturbations include lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular disease (CVD), all of which are strongly linked epidemiologically to cigarette smoking. In this review, we highlight the significance of genomics and epigenomics in these major smoking-related diseases. We also summarize the in vitro and in vivo findings on the specific perturbations that smoke and its constituent compounds can inflict upon the genome, particularly on the pulmonary system. Finally, we review state-of-the-art genomics and new techniques such as high-throughput sequencing and genome-wide chromatin assays, rapidly evolving techniques which have allowed epigenetic changes to be characterized at the genome level. These techniques have the potential to significantly improve our understanding of the specific mechanisms by which exposure to environmental chemicals causes disease. Such mechanistic knowledge provides a variety of opportunities for enhanced product safety assessment and the discovery of novel therapeutic interventions.
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Talikka
authors.forename: N
authors.initials: N
authors.lastname: Sierro
authors.forename: N V
authors.initials: NV
authors.lastname: Ivanov
authors.forename: N
authors.initials: N
authors.lastname: Chaudhary
authors.forename: M J
authors.initials: MJ
authors.lastname: Peck
authors.forename: J
authors.initials: J
authors.lastname: Hoeng
authors.forename: C R E
authors.initials: CR
authors.lastname: Coggins
authors.forename: M C
authors.initials: MC
authors.lastname: Peitsch
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic / Q000187:drug effects; D057890:Epigenomics; D006801:Humans; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects
chemical_list: D002843:Chromatin; D012906:Smoke