Toenail clippings may be among the most accurate indicators of lung cancer, according to a new study from UCSD Medical Center and the Harvard School of Public Health.

The study found that men with higher levels of nicotine in their toenails were more likely to develop lung cancer, whether they were smokers or non-smokers. While nicotine is not a carcinogen, high exposure to nicotine is generally correlated with high exposure to carcinogens in tobacco, leading to lung cancer.

Lung cancer is determined largely by long-term exposure to nicotine, which urine and saliva samples are unable to capture.

Wael Al-Delaimy of UCSD and Walter Willet of Harvard conducted a joint study that found that toenails, which retain nicotine for a longer period of time, may be the best biomarker for predicting lung cancer.

“Because toenails grow very slowly, they represent exposure of a person to tobacco over a longer period of time,” Al-Delaimy said. “And that gives us the advantage of [acquiring] a longer-term exposure rather than just in the last few days like other biomarkers do. So this can give us exposure on average for the last twelve months.”

The cohort study followed men aged 40 to 75 from 1987 to 2000. The study used a nested case-control design, which identifies cases of lung cancer that occur in a group of people while also selecting from another group of people that have not yet developed the disease.

In the study, toenail samples were taken before patients developed lung cancer and were analyzed after they developed the cancer. Researchers took toenail samples from 210 men who developed lung cancer during a 12-year follow-up and 630 men who did not develop.

To determine nicotine levels, the toenail samples were chemically processed in a lab and then quantified through a chromatogram to show the nicotine levels in the samples compared to an internal standard. The results were then used to rank the people who gave the toenail samples according to their exposure levels.

The researchers found that people who had lung cancer had high nicotine levels in their toenails compared to those who did not. They then statistically analyzed the results, which showed that even among non-smokers, those with higher nicotine levels from secondhand smoke were likelier to develop lung cancer.