Scientists in the US may have uncovered why some smokers get lung cancer while others do not: they found that those with the highest urine levels of a known biomarker for the uptake of a cancer-causing chemical found in tobacco had a two-fold increased risk of developing lung cancer than those with the lowest levels.
The study was the work of Dr Jian-Min Yuan, associate professor of public health at the University of Minnesota, and colleagues, and is being presented at the 100th Annual Meeting of the American Association for Cancer Research, which is taking place from 18 to 22 April, at the Colorado Convention Center in Denver.
“A history of smoking has always been thought of as a predictor of lung cancer, but it is actually not very accurate,” said Yuan, explaining in a press statement that the big question that has been challenging researchers is why it raises risk in some people and not others.
Studies have shown that the chemical NNAL, a metabolic byproduct of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, induces lung cancer in laboratory animals, but we don’t know what it does to humans.
Yuan and colleagues wanted to find out if the amount of NNAL in the urine of humans might predict their risk of lung cancer.
To do this they used data from two large cohort studies: the Shanghai Cohort Study which covers 18,244 men, and the Singapore Chinese Health Study, which coveres 63,257 men and women. These studies included personal interviews to assess diet, lifestyle, levels of cigarette smoking, and results of blood and urine analysis from over 50,000 people.
From these records Yuan and colleagues found 246 current smokers who later developed lung cancer and matched them with 245 smokers who did not develop lung cancer during the ten years that ensued after they enrolled in the studies and gave their interviews and samples.
They grouped the participants according to the level of NNAL found in their urine samples and looked for links between these and risk of lung cancer, after taking into account other possible influencers such as number of cigarettes smoked per day, how long they had been smoking, and the amount of cotinine (a metabolite of nicotine) in their urine.
The researchers found that those smokers with the highest levels of NNAL had double the risk of developing lung cancer than those with the lowest levels. Smokers with a mid-range level had 43 per cent higher risk than those with the lowest levels of NNAL.
They also found that those smokers with the highest levels of nicotine and NNAL in their urine had a 8.5 times higher risk of developing lung cancer than those with the lowest levels, regardless of how long they had been smoking for.
Yuan said while we know smoking leads to lung cancer, there are over 60 potential cancer causing chemicals in tobacco smoke, and “the more accurately we can identify the culprit, the better we will become at predicting risk”.
According to the World Health Organization, lung cancer is the most common cancer worldwide, accounting for 1.2 million new cases annually. It is also the biggest cause of death by cancer, responsible for 17.8 per cent of all cancer deaths.
80 per cent of lung cancer cases in men are caused by smoking, whereas in women the rate is 45 per cent worldwide but more than 70 per cent in North America and Northern Europe. In both men and women the incidence is low for the under 40s, but climbs steadily until the age of 70-75.
The rise in lung cancer in women is a particular concern, and in the US, more women die from smoking-induced lung cancer than from breast cancer, according to the WHO.
Sources: American Association for Cancer Research, WHO.
Written by: Catharine Paddock, PhD