Non-smokers, but still at risk: the new face of lung cancer

For years, we have clung to the certainty of a simple and reassuring story: lung cancer, the global big killer, only affects heavy smokers. If you don't smoke, you are safe. But the reality, as is often the case in medicine, is much more complex. And given that cigarette smoking according to the WHO is directly responsible for 7 out of 10 lung cancers among males, 'blondes' alone do not explain the whole story. Thus, while the statistics on smoking habit show a negative trend, because anti-smoking campaigns are evidently working (but also because of the inexorable rise of 'electronic' alternatives to tobacco), another statistic is quietly growing: that of lung cancer cases in non-smokers.

This is not a paradox, but a change of scenario and greater scientific awareness, which is increasingly bringing this new reality to the fore. And a study just published in Trends in Cancer, signed by Deborah Caswell of University College London and colleagues, reminds us very clearly: being a non-smoker does not mean being 'immune' from lung cancer.

Lung cancer in non-smokers is a 'different' disease from that caused by the number one defendant, smoking. In many respects, it is a different entity, with its own biological characteristics and specific clinical behaviour. But above all, it is burdened by a huge problem: it comes very late to diagnosis. Partly because, being unfamiliar with cigarettes, one does not think one might develop the problem. And one therefore pays no attention to those vague, everyday, almost trivial symptoms. A cough that does not go away (after months), persistent tiredness, some discomfort in swallowing. For those who have never smoked, these signs rarely set off alarm bells in the person concerned, but often also in the treating doctor. Rather, one thinks of an infection, stress, perhaps gastro-oesophageal reflux or a passing disorder. And so time passes. And when the disease is finally given a name, it is often in an advanced stage, when the chances of recovery are very slim.

The good news is that research is making great strides in understanding the causes of this 'alternative' lung cancer and its biology. Air pollution (especially from PM2.5 particulate matter) is one of the main suspects, along with exposure to radon - a naturally occurring radioactive gas that can accumulate in the home - passive smoking (increases the risk by 20-25%) and ionising radiation, a chapter in the big book of 'risk' that goes by the name of the exposome. Added to these environmental factors is the frequent presence of a number of inherited genetic variants in oncogenes and genes responsible for the DNA damage response, which may make some people more vulnerable. Last but not least, an association is emerging between this type of cancer and the presence of certain inflammatory conditions (gastro-oesophageal reflux, respiratory infections of the first airways, certain viral infections, Bpco).

In light of this new awareness, a paradigm shift is needed. Prevention and screening strategies designed for heavy smokers (such as low-dose CT scanning) cannot be transferred tout court to non-smokers; a targeted approach is needed, capable of identifying subgroups at risk (e.g. by monitoring radon and exposure to particulate pollution, using the postcode), within a population that, by definition, does not fall within traditional risk criteria within a population that, by definition, does not fit the traditional risk criteria. As an example, the demography of lung cancer in non-smokers is also anomalous: it is more frequent among women (more than twice as many men are affected by this type of cancer) and among Asian populations.