Damage to DNA by tobacco-specific nitrosamines predicts head and neck cancer risk, study finds

August 18, 2017

Findings could help determine who’s most at risk for head, neck cancer and inform  tobacco patients’ treatment

MINNEAPOLIS/St. PAUL (August 18, 2017) – DNA damage in the mouth caused by  carcinogens found in tobacco (known as tobacco-specific nitrosamines) may predict which tobacco users will develop oral/head and neck cancer, according to a new study published in the journal Cancer Prevention Research.

The study, led by Samir Khariwala, MD, and Irina Stepanov, PhD, of the Masonic Cancer Center, University of Minnesota, points to a future when physicians could swab the inside of tobacco users’ cheek to analyze risk so they’re better able to address smokers who have been unsuccessful in quitting.

“It’s well known that tobacco is dangerous and causes a variety of cancers, along with myriad other medical problems.  Because of this, all smokers must be urged and helped to quit.” said Khariwala, Associate Professor within the University of Minnesota Medical School’s Department of Otolaryngology-Head and Neck surgery. “But this is the first time that tobacco-related DNA damage has been directly assessed at the site of injury in the mouth.  We have found that some smokers, those who have gone on to develop cancer, have greater levels of DNA damage than smokers without cancer.”

Previous studies that analyzed tobacco nitrosamine biomarkers in urine already showed that such exposures are predictive of cancer development in the lung and esophagus. However, less is known about the predictors of oral/head and neck cancer (OHNC), which affects about one in every 100 smokers. The University of Minnesota researchers used the cutting-edge technology, called high-resolution mass-spectrometry, to explore nitrosamine-related DNA damage in the small amounts of DNA extracted from the mouth tissue to see if it would provide information about the risk of OHNC.

Khariwala, Stepanov and colleagues observed 30 smokers with OHNC and 35 smokers without OHNC. Participants were only eligible if they self-identified as daily smokers who smoked at least five cigarettes per day for at least five years. The investigators ensured that both groups had similar exposure to tobacco and carcinogens.

The analysis showed those with OHNC had a significantly higher level of nitrosamine-related DNA damage compared to the smokers without cancer. While the precise explanation for this finding is not yet known, the results suggest that smokers differ in how they process cancer-causing chemicals that are present in cigarette smoke, and how the damage that these chemicals cause to DNA is repaired, ultimately changing their risk of developing tobacco-induced tumors.

“Biomarkers can play a vital role in measuring important changes in cells and DNA that eventually lead to disease, and the technologies for biomarker measurements are becoming more and more sensitive. We are fortunate to have access to the advanced mass-spectrometry equipment in the Masonic Cancer Center, and we have outstanding scientists like Dr. Bin Ma, the member of my laboratory who developed the unique methodology for this study,” added Stepanov, Associate Professor within the University of Minnesota School of Public Health. “Using this research as a building block, we hope to confidently understand how the tobacco-induced DNA damage contributes to oral cancer. Such knowledge can help to move beyond detecting risk factors to finding new approaches for cancer prevention.”

This research was supported by National Institute of Dental and Craniofacial Research K23DE023572 and the National Cancer Institute R01 CA180880, both affiliated with the National Institutes of Health.