News | Science Selections July 2014 | Volume 122 | Issue 7
Building a Solid Case: Cigarette Smoking and Epigenomic Alterations
Wendee Nicole was awarded the inaugural Mongabay Prize for Environmental Reporting in 2013. She writes for Discover, Scientific American, National Wildlife, and other magazines.
Related EHP Article
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.2
CpG 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.
“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.
1. 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].
2. Harlid S, et al. CpG sites associated with cigarette smoking: analysis of epigenome-wide data from the Sister Study. Environ Health Perspect 122(7):673–678 (2014); doi: 10.1289/ehp.1307480.
3. 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].
4. Shenker NS, et 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):843–851 (2013); doi: 10.1093/hmg/dds488.
EHP is pleased to announce that Prenatal Exposure to Glycol Ethers and Neurocognitive Abilities in 6-Year-Old Children: The PELAGIE Cohort Study, published in EHP on 14 October 2016, has been selected by the Children’s Environmental Health Network (CEHN) as its May 2017 Article of the Month. CEHN Article of the Month summaries discuss the potential policy implications of current children’s environmental health research. The CEHN summary can be viewed here.
Among the Resources now available on our Children’s Health page is the text of Executive Order 13045, “Protection of Children from Environmental Health Risks and Safety Risks” (21 April 1997). The Executive Order noted the particular vulnerabilities of children to environmental hazards, codified the need to identify and alleviate such risks, and created the President’s Task Force on Environmental Health Risks and Safety Risks to Children to identify data resources and promote research in these areas. As we mark 20 years since the order was enacted, we can see how these efforts have produced important research and mitigation of hazards—a strong base for continued work on behalf of children’s environmental health.
EHP is excited to announce that, starting later in May 2017, the journal will transition from a traditional, issue-by-issue publishing model, to a new, article-by-article publishing model known as continuous publication. This is a more modern way of publishing an online journal, and one that should help to significantly improve EHP’s time to publication. (more…)