Building a solid case: cigarette smoking and epigenomic alterations.

Abstract

Vol. 122, No. 7 News | Science SelectionsOpen AccessBuilding a Solid Case: Cigarette Smoking and Epigenomic Alterationsis accompanied byCpG Sites Associated with Cigarette Smoking: Analysis of Epigenome-Wide Data from the Sister Study Wendee Nicole Wendee Nicole Search for more papers by this author Published:1 July 2014https://doi.org/10.1289/ehp.122-A194View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Smoking is a leading cause of premature death and disease worldwide,1 but figuring out just how it causes cancer and other diseases has proven more challenging. Several recent studies have shed light on one possible answer: Smoking modifies the epigenome, changing methylation patterns of genes, which in turn can alter gene expression. In this issue of EHP, a team of researchers at the National Institute of Environmental Health Sciences not only corroborates smoking-related associations previously reported for a number of CpG sites but also identifies new sites.2CpG sites are cytosine and guanine nucleotides separated by a single phosphate that are found in gene promoter regions. Over the past few years, epigenome-wide association studies have suggested that smoking alters the methylation patterns of a number of CpG sites across the human genome.Epigenome-wide association studies are zeroing in on a number of CpG sites whose methylation patterns appear to be altered in response to smoking.© ArtBitz/Shutterstock“When a cell divides, the daughter cell copies the methylation marks that the original cell had, and that can continue to influence whether a gene is transcribed even though the primary DNA sequence is not altered,” says Jack Taylor, head of the NIEHS Molecular and Genetic Epidemiology Section, who oversaw the study. If an environmental exposure can alter the epigenetic profile of the DNA, in turn influencing which genes are transcribed and affecting risk of disease, “that’s a big deal,” Taylor says.In the current paper, the authors compared DNA methylation and history of cigarette smoking using data collected from the NIEHS Sister Study.3 This landmark project involves a cohort of more than 50,000 women whose sisters were previously diagnosed with breast cancer.The study confirmed smoking-related associations for 10 previously identified CpG sites. Two CpG sites of particular interest are located on the AHRR and CPOX genes. AHRR is a tumor suppressor that also detoxifies polyaromatic hydrocarbons and regulates metabolism of dioxin, while the CPOX gene is involved in synthesis of heme (a component of hemoglobin). Smoking is known to increase heme synthesis, and the authors theorize that smoking might lead to increased expression of this gene and altered methylation.“The Taylor article is a good addition to the body of evidence to support the previously identified markers, and identifies two new loci that could be of important biological interest,” says Natalie Shenker, a clinical researcher in the Epigenetics Unit at Imperial College London. “These two loci were also on our list of top hits,4 but did not reach the stringent cut-off for significance in our statistical analysis.”The current study found that all 12 CpG sites identified showed a consistent trend of increasingly altered methylation from current smokers to past smokers to never-smokers, suggesting that methylation patterns may self-restore to some extent after a person quits. It also provides further evidence that DNA methylation patterns may serve as accurate long-term biomarkers for smoking.References1 CDC. How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. A Report of the Surgeon General. Atlanta, GA:National Center for Chronic Disease Prevention and Health Promotion, U.S. Centers for Disease Control and Prevention (2010). Available: http://www.ncbi.nlm.nih.gov/books/NBK53017/ [accessed 11 June 2014]. Google Scholar2 Harlid Set al.CpG sites associated with cigarette smoking: analysis of epigenome-wide data from the Sister Study.Environ Health Perspect 122(7):673-6782014.; doi:10.1289/ehp.130748024704585. Link, Google Scholar3 The Sister Study [website]. Research Triangle Park, NC:National Institute of Environmental Health Sciences, National Institutes of Health. Available: http://sisterstudy.niehs.nih.gov/ [accessed 11 June 2014]. Google Scholar4 Shenker NSet al.Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking.Hum Mol Genet 22(5):843-8512013.; doi:10.1093/hmg/dds48823175441. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsRelated articlesCpG Sites Associated with Cigarette Smoking: Analysis of Epigenome-Wide Data from the Sister Study4 April 2014Environmental Health Perspectives Vol. 122, No. 7 July 2014Metrics About Article Metrics Publication History Originally published1 July 2014Published in print1 July 2014 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.