Genomics and the ‘healthy smoker’

While smoking is undoubtedly associated with disease, there are smokers who escape. Are they just lucky?

As every health professional knows, smoking tobacco is undoubtedly harmful to human health; it is arguably the foremost common environmental ‘lifestyle’ factor associated with disease. Not surprisingly, this particularly applies to diseases of the lungs, both lung cancer and chronic obstructive pulmonary disease (COPD) – an umbrella term for a group of diseases that narrow the airways and impede breathing, including emphysema, chronic bronchitis and obstructive airways disease.

Smoking, disease and health

COPD is thought to affect over three million people in the UK, and is a major cause of morbidity due to symptoms of increasing breathlessness, coughing and frequent chest infections. Smoking increases the risk of developing COPD, and may account for around half of all cases worldwide, making it the third leading cause of smoking-related deaths globally after lung cancer and cardiovascular disease. Smoking also increases the risk of lung cancer, accounting for 85-90% of cases.

However, just as many smokers never develop lung cancer, many also never develop COPD and continue to have healthy lung function – in some cases well into old age. This anomaly is of interest to scientists and clinicians worldwide, and genomics is playing a vital role in understanding it.

A lucky genome?

A new study from 100,000 Genomes Project partners UK Biobank – a pioneering population health study based on half a million older UK citizens – has examined the genetic links between smoking behaviours and lung health. It seems that so-called ‘healthy smokers’ are indeed lucky – but at least some of that luck lies in their genomes.

50,000 participants who were either heavy smokers or had never smoked were selected for the study. Their DNA was then scrutinised for 28 million gene variants, enabling scientists to compare the genomes of the smokers and the non-smokers, as well as comparing healthy individuals with those with COPD. Researchers identified a number of new genetic variants associated with healthy lung function. When present, these genetic features gave some protection against COPD even in heavy smokers – probably by affecting the lung tissue’s inflammatory response to the irritation from tobacco smoke. Insights of this kind can help to unravel just how the lungs work in health and disease; and understanding that can in turn potentially lead to the development of new treatments.

A smoker’s brain?

The researchers also identified new genetic variants which they think could affect the way in which the brain responds to nicotine – the addictive component of tobacco smoke – and therefore the probability of heavy smoking. Unpicking genes that affect the brain’s response to nicotine and influence behaviour may make the underlying causes of nicotine addiction clearer, hopefully aiding the design of more tailored and effective interventions to help people stop smoking.

British Lung Foundation’s Head of Research Ian Jarrold told the BBC: “Understanding genetic predisposition is essential in not only helping us develop new treatments for people with lung disease but also in teaching otherwise healthy people how to better take care of their lungs.”

The bottom line is that taking care of our lungs is important for everyone. Although there are some heavy smokers whose genomes give them a degree of protection against airway disease, their risk of COPD (not to mention lung cancer and cardiovascular disease) would nevertheless be much lower if they didn’t smoke – and not smoking is still the best choice most of us can make to protect our health.