Biomarker discovered that measures the risk of cancer in non-smokers

Researchers from the Hospital del Mar Medical Research Institute (IMIM) have, for the first time, demonstrated that measurements of a tobacco-specific nitrosamine in the hair, NNK, correlate with the real risk of exposure to the carcinogens in tobacco smoke in passive smokers. This substance is a much better biomarker than any of the markers measured up to now for assessing this risk and it has been found in higher concentrations in the hair than any other tobacco-specific carcinogen. The study was conducted in collaboration with researchers at the Catalan Institute of Oncology (ICO) and has been published in the journal Scientific Reports.

The smoke passive smokers are exposed to differs from the smoke of smokers. Passive smokers are exposed to a lot of chemicals resulting from the combustion of the cigarette, but in addition, certain substances have gone through various activation reactions, making them carcinogenic. This is what is known as second- and third-hand smoke. "Being able to directly measure these carcinogenic nitrosamines, especially the NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone), means we have very useful information for assessing the real risk of exposure to those substances that can cause DNA damage and, therefore, originate cancer", explains Dr. José Antonio Pascual, a researcher in the Neurosciences programme at the IMIM.

According to Dr. Pascual, "this is the first study to demonstrate that NNK is present in hair samples from non-smokers, even those who do not feel they are exposed to tobacco smoke. NNK is present in higher concentrations than other tobacco-specific nitrosamines."

The hair is a biological matrix that is excellent for measuring various substances as well as real average and cumulative exposure over time. Because of its growth characteristics (around 1 cm/month) it can accumulate substances over long periods, enabling both the study and the timeline reconstruction for tobacco consumption.

This research group has been looking at several substances in human hair deriving from tobacco consumption -nicotine, cotinine, and the nitrosamines NNK, NNN, and NNAL– and how these accumulate in this biological matrix. "We have found that the concentrations of these substances differ between non-smokers according to their level of exposure to the smoke", explains Dr. José Antonio Pascual. The study also detected other carcinogens such as NNN, although NNAL is absent in hair. NNK shows a moderate correlation with the levels of nicotine and cotinine found, although NNN did not correlate with the other substances analysed, suggesting a different origin.

Cotinine, the main biotransformation product of nicotine, is the most typically employed smoke-exposure marker, and its levels correlate well with the true quantity of cigarettes consumed. It is therefore a good marker for "the truth" about consumption or exposure not consciously perceived by smokers. However, in passive smokers the levels of cotinine are not as useful as exposure markers because they underestimate the risk of developing cancer in non-smokers exposed to cigarette smoke, by mixing direct combustion smoke with second or third hand smoke. It is necessary to measure the by-products of transformation processes, like the derived nitrosamines – NNK, NNN and NNAL- that do not have such a close relationship with nicotine, but depend on the type of exposure and how each person produces them, either from tobacco consumption or exposure.

Reference article

Pérez-Ortuño R, Martínez-Sánchez JM, Fu M, Fernández E, Pascual JA*. Evaluation of tobacco specific nitrosamines exposure by quantification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human hair of non-smokers. Sci Rep 2016; 6: 25043.