News | Science Selection Volume 122 | Issue 7 | July 2014
Environ Health Perspect; DOI:10.1289/ehp.122-A194
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.
ISEE 2015 Abstracts Now AvailableEHP is pleased to present the abstracts for the 2015 annual conference of the International Society for Environmental Epidemiology (ISEE), “Addressing Environmental Health Inequalities,” held 30 August–3 September 2015 in São Paulo, Brazil.
New Editor-in-ChiefWe are pleased to announce that Sally Perreault Darney has been selected as the new Editor-in-Chief of EHP. Sally comes to EHP from the U.S. Environmental Protection Agency, where she most recently co-led a large research project focused on assessing health disparities in vulnerable groups and providing healthy environments for children. Learn more about Sally and her vision for the journal in the September issue of EHP.
Sign Up to Receive E-mail Alerts
Recent Advance Publications
A Curated Database of Rodent Uterotrophic Bioactivity
Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts
E-Waste and Harm to Vulnerable Populations: A Growing Global Problem
Organophosphate Insecticide Metabolites in Prenatal and Childhood Urine Samples and Intelligence Scores at 6 Years of Age: Results from the Mother-Child PELAGIE Cohort (France)
Organophosphate Pesticide Exposures, Nitric Oxide Synthase Gene Variants, and Gene–Pesticide Interactions in a Case-Control Study of Parkinson’s Disease, California (USA)