@tobaccoresearch and visit TReND’s web portal for content updates: www.tobaccodisparities.org
FDA Center for Tobacco Products
WHO Framework Convention on Tobacco Control
TReND: In Vitro Assessment of the Potential Interactive Effects of Tobacco Smoke and Lifestyle and Environmental Agents
Visit TReND’s web portal www.tobaccodisparities.org to learn more about research, programs, policies, and resources relevant to tobacco and health disparities.
Return to TReND Projects
Rationale: Determinants of tobacco-related health disparities (TRHDs) are not clearly understood. The contribution of biological factors may be important. Current efforts to determine biological differences in tobacco use and related diseases among racial classified social groups (RCSGs) have primarily focused on genetic variations. However, this approach has limitations. An alternative framework of analysis to the genetic approach is a biopsychosocial one that examines the potential biological mechanisms through which life experiences and behavior might affect tobacco use and health outcomes in these population groups. The biological activities of several factors suggest their potential to affect the biological pathways involved in tobacco use and, thereby, modulate its effects. These factors include those of lifestyle (e.g., diet/nutrition, obesity, physical exercise, alcohol consumption), psychological (e.g., stress and coping), occupational/environmental exposures, and the presence of other diseases/illnesses.
Purpose: The goal of this project is to provide scientific evidence supporting a model of interactive effects of multiple factors on the biological pathways of tobacco-induced diseases. More specifically, the objective is to assess in vitro the potential for interactive effects of tobacco smoke and various lifestyle and environmental agents on DNA methylation status. DNA methylation is an important etiological pathway in tobacco-induced diseases. The central hypothesis is that tobacco smoke induces DNA methylation of genes known to be involved in the genesis of lung cancer and that lifestyle and environmental agents modulate the effect of tobacco smoke. We plan to test our hypothesis by:
- Determining the effect of cigarette smoke condensate (CSC) on DNA methylation of several genes in lung cells; and
- Assessing the ability of other agents, including folate, genistein, selenium, ethanol, arsenic, and nickel, to modulate the effect of CSC on gene DNA methylation, either singularly or in various combinations.
Impact: Results from this study will provide important data for support of population-based studies to assess the contribution of interactive effects of lifestyle and environmental factors with tobacco use to differential tobacco-related health outcomes among RCSGs. A clearer understanding of the impact of psychosocial and environmental factors, which can act individually and interactively, on biological pathways involved in tobacco use and contribute to disparities in tobacco-related outcomes can provide an important contribution and foundation for developing appropriate interventions.
George Hammons, PhD (Principal Investigator)
Philander Smith College
Anita Fernander, PhD
University of Kentucky
Beverly Lyn-Cook, PhD
Food and Drug Administration (FDA), National Center for Toxicological Research
Bibi Mwamba, Student Trainee
Philander Smith College
George Hammons, PhD
Professor and Chair
Department of Chemistry
Philander Smith College
Not available yet
Baccerilli A, Bollati V (2009). Epigenetics and environmental chemicals. Curr Opin Pediatr; 21: 243-251.
Beleford D, Liu Z, Rattan R, et al (2010). Methylation induced gene silencing of HtrA3 in smoking-related lung cancer. Clin Cancer Res; 16: 398-409.
Bollati V, Baccarelli A, Hou L, et al (2007). Changes in DNA methylation patterns in subjects exposed to low-dose benezene. Cancer Res; 67: 876-880.
Dolinoy DC, Jirtle RL (2008). Environmental epigenomics in human health and disease. Environ Mol Mutagen; 49: 4-8.
Fernander AF, Shavers VL, Hammons GJ (2007). A biopsychosocial approach to examining tobacco-related health disparities among racial classified social groups. Addiction; 102(Suppl. 2):43-57.
Fernander AF (2007). Racially classified social group tobacco-related health disparities: what is the role of genetics? Addiction; 102(Suppl. 2): 58-54.
Flenaugh EL, Henriques-Forsythe MN (2006). Lung cancer disparities in African Americans: Health versus health care. Clin Chest Med, 27, 431-439.
Fraga, MF, Ballestar E, Paz MF (2005). Epigenetic differences arise during the lifetime of monozygotic twins. PNAS; 102: 10604-10609.
Gomes MV, Waterland RA (2008). Individual epigenetic variation: When, why, and so what? Nestle Nutr Workshop Ser Pediatr Program; 62: 141-162.
Hammons GJ, Yan Y, Lopatina NG, et al (1999). Increased expression of hepatic DNA methyltransferase in smokers. Cell Biol Toxicol; 15: 389-394.
Herceg Z (2007). Epigenetics and cancer: Towards an evaluation of the impact of environmental and dietary factors. Mutagenesis; 22: 91-103.
Izzotti A, Calin GA, Steele VE, et al (2010). Chemoprevention of cigarette smoke-induced alterations of MicroRNA expression in rat lungs. Cancer Prev Res, 3, 62-72, 2010.
Jones PA, Baylin SB (2002). The fundamental role of epigenetic events in cancer. Nat Rev Genet; 3: 415-428.
Kerr KM, Galler JS, Hagen JA, et al (2007). The role of DNA methylation in the development and progression of lung adenocarcinoma. Disease Markers; 23: 5-30.
Kuzawa CW, Sweet E (2009). Epigenetics and the embodiment of race: developmental origins of US racial disparities in cardiovascular health. Am J Human Biology; 21: 2-15.
Laird PW (2010). Principles and challenges of genome-wide DNA methylation analysis. Nat Rev Genet; 11: 191-203.
Laird PW, Jaenisch R (1996). The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet; 30: 441-464.
Lin R-K, Hsieh Y-S, Lin P, et al (2010). The tobacco-specific carcinogen NNK induces DNA methyltransferase 1 accumulation and tumor suppressor gene hypermethylation in mice and lung cancer patients. J Clin Investigation; 120: 521-532.
Lyn-Cook BD, Blann E, Payne PW, et al (1995). Methylation profile and amplification of proto-oncogenes in rat pancreas induced with phytoestrogens. Proc Soc Exp Biol Med; 208: 116-119.
Marsit CJ, Kim D-K, Liu M, et al (2005). Hypermethylation of RASSF1A and BLU tumor suppressor genes in non-small cell lung cancer: Implications for tobacco smoking during adolescence. Int J Cancer; 114: 219-223.
Peng D-F, Kanai Y, Sawada M, et al (2006). DNA methylation of multiple tumor-related genes in association with overexpression of DNA methyltransferase 1 (DNMT 1) during multistage carcinogenesis of the pancreas. Carcinogenesis; 27: 1160-1168.
Rajendrasozhan S, Yao H, Rahman I (2009). Current perspectives on role of chromatin modifications and deacetylases in lung inflammation in COPD. COPD; 6: 291-291.
Russo AL, Thiagalingam A, Pan H, et al (2005). Differential DNA hypermethylation of critical genes mediates the stage-specific tobacco smoke-induced neoplastic progression of lung cancer. Clin Cancer Res; 11: 2466-2470.
Schembri F, Sridhar S, Perdomo C, et al (2009). MicroRNAs as modulators of smoking-induced gene expression changes in human airway epithelium. PNAS; 106: 2319-2324.
Schwartz AG, Prysak GM, Bock CH (2007). The molecular epidemiology of lung cancer. Carcinogenesis; 28: 507-518.
Shavers VL, Shavers BS (2006). Racism and health inquiry among Americans. JNMA; 98:386-390.
Stidley AC, Picchi MA, Leng S, et al (2010). Multivitamins, folate, and green vegetables protect against gene promotor methylation in the aerodigestive tract of smokers. Cancer Res; 70: 568-574.
Szyf M (2009). The early life environment and the epigenome. Biochim Biophys Acta; 1790: 878-885.
Toyooka S, Maruyama R, Toyooka KO, et al (2003). Smoke exposure, histologic type and geography-related differences in the methylation profiles of non-small cell cancer. Int. J. Cancer; 103, 153-160.
Vaissiere T, Hung RJ, Zaridze D, et al (2009). Quantitative analysis of DNA methylation profiles in lung cancer identifies aberrant DNA methylation of specific genes and its association with gender and cancer risk factors. Cancer Res; 69: 243-252.
Veeck J, Esteller M (2010). Breast cancer epigenetics: From DNA methylation to microRNAs. J Mammary Gland Biol Neoplasia; 15: 5-17.
Zhang L, Lee JJ, Tang H, et al (2008). Impact of smoking cessation on global gene expression in the bronchial epithelium of chronic smokers. Cancer Prev Res; 1: 112-118
The National Cancer Institute (NCI) and American Legacy Foundation are proud to fund the Tobacco Research Network on Disparities (TReND). Previous support has also been provided by the Department of Health and Human Services (DHHS) Office on Women’s Health, NCI Office of Women’s Health, and the NCI Center to Reduce Cancer Health Disparities.