New research published in JAMA Oncology shows that DNA damage that occurs as a result of smoking may be found in cheek swabs. In light of this research, smoking is thought to adjust the epigenetic profile of cheek cells and the resulting epigenetic landscape may even be used as an early warning sign of other cancers typically unrelated to smoking, such as gynecological and breast cancers.
Professor Martin Widschwendter, Head of the Department of Women’s Cancer at the UCL Institute for Women’s Health led the study along with Dr. Andrew Teschendorff of the UCL Cancer Institute. They assessed epigenetic alterations made to DNA which are known to affect gene expression by either turning genes on or off. Cancer development has long been associated with epigenetic modifications such as DNA methylation and histone modifications. Environmental exposures, for instance cigarette smoke, are often connected to the development of cancer via epigenetic mechanisms.
The team set out to determine whether or not normal cheek cells would show epigenetic changes commonly linked to lung cancer and other epithelial cancers as a result of smoking. In the UK, epithelial cancer is estimated to account for 85% of cancer incidences. Epithelial cancers begin in the epithelial cells which consist of skin outside the body as well as lining of the internal body cavities and organs. The cells collected from cheek swabs, known as buccal cells, are ideal to study because they’re simple and easy to acquire and come in direct contact with cigarette smoke.
They analyzed 790 samples of buccal cells from women and 152 matched blood samples. The dataset they used contained information regarding current and past smoking status.
Their study demonstrated that the women’s buccal cells exposed to cigarette smoke had a lot of epigenetic alterations made to their DNA, particularly by the epigenetic mechanism called DNA. DNA methylation is defined as the addition of a methyl group (CH3) to cytosine, often resulting in gene suppression.
The research team found that buccal cells demonstrated a 40-fold increase in aberrant DNA methylation sites in comparison to the corresponding blood samples. This significant increase in methylation status compared to the normal blood samples, referred to as differentially methylated regions, supports the idea that DNA is subjected to negative epigenetic changes as a result of smoking.
Essentially, smoking is thought to impact the epigenome in a negative way such that the genetic code is harder if not impossible to read. The cells are unable to form properly or differentiate like they’re supposed to because of these epigenetic modifications occurring as a result of harmful environmental factors, for instance smoking. Differentiation is known as the transitioning of one cell type to another typically for that cell to become more highly specialized. Cancer is able to spread to other parts of the body because the cells are trapped in their undeveloped, non-differentiated state.
The group of scientists expanded on their findings and analyzed the epigenetic “program” or epigenetic profile linked to cigarette smoke in over 5,000 tissue samples. These tissues included normal ones, pre-cancerous, and cancerous from a variety of different epithelial cancers. The epigenetic profile they identified initially from the buccal cells is capable of distinguishing between cancerous and normal tissue with nearly 100% sensitivity and 100% specificity regardless of which organ the cancer came from.
They also were able to calculate what would come of pre-invasive cancer lesions by seeing whether or not the same epigenetic changes were present. If the DNA methylation changes were present in the cells, then it was likely that invasive cancer would develop. The absence of these DNA methylation tags, however, made it more likely that the pre-cancer would regress or go away entirely.
Professor Martin Widschwendter said that we’re much closer to unravelling the mysteries of how environmental factors lead to cancer. These recent findings set the stage for other epigenetic research “in which easily accessible cells can be used as proxies to highlight epigenetic changes that may indicate a risk of developing cancer at a site where cells are inaccessible.”
He also indicated that because cancer risk is difficult to predict for women’s cancers such as endometrial, ovary, and breast, the team’s discovery brings us closer to predicting cancer risk in these challenging cases. Using buccal cells instead of blood provides a more accessible alternative to cancer risk assessment and will be especially useful for conducting epigenome-wide association studies (EWASs) for epithelial cancers related to smoking.
Lead author Andrew Teschendorff commented, “Our work shows that smoking has a major impact on the epigenome of normal cells that are directly exposed to the carcinogen. Of particular significance is that these epigenetic changes are also seen in both smoking-related and non-smoking related cancers, pointing towards a universal cancer landscape. This research gets us closer to understanding the very first steps in carcinogenesis and in future may provide us with much-needed tests for risk prediction and early detection.”
Professor Widschwendter also commented on the reversibility of these epigenetic modifications: “The results also demonstrate that smoking-related DNA damage to the epigenome of certain genes had been reversed in ex-smokers who had quit 10 years previously before sample collection, highlighting the key health benefits of quitting smoking, or not taking it up at all.”
Source: Andrew E. Teschendorff, Zhen Yang, Andrew Wong, Christodoulos P. Pipinikas, Yinming Jiao, Allison Jones, Shahzia Anjum, Rebecca Hardy, Helga B. Salvesen, Christina Thirlwell, Samuel M. Janes, Diana Kuh, Martin Widschwendter. Correlation of Smoking-Associated DNA Methylation Changes in Buccal Cells With DNA Methylation Changes in Epithelial Cancer. JAMA Oncology, 2015.
Reference: UCL Cancer Institute (2015). Smoking induces early signs of cancer in cheek swabs. UCL Cancer Institute News. 14 May 2015.
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