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Breast cancer gene and smoking is a 'lethal mix'

“Smoking and the breast cancer risk gene BRCA2 combine to ‘enormously’ increase the chance of developing lung cancer,” BBC News reports.

The BRCA2 gene, which is known to increase breast cancer risk, appears to also up the risk of lung cancer in smokers.

A new study analysed the genetic make-up of more than 10,000 people with lung cancer to identify genetic and lifestyle risk factors for the disease.

One of the genetic variants they identified was linked to the BRCA2 gene and increased a person’s risk of having lung cancer – specifically, squamous cell carcinoma – by 2.47 times.

This may have important implications for identifying who should undergo lung cancer screening, especially those considered to be high risk.

But cancer involves the accumulation of genetic damage in many gene regions rather than just one, so identifying these single genetic risks is not the full picture.

In addition to genetic risks, which you can’t change, there are lifestyle risk factors, the biggest of which is smoking.

If you smoke, you are significantly increasing your risk of developing lung cancer later in life. And it seems that if you also have the BRCA2 gene variant, the risks may be even greater.

The results of this study reinforce the dangers of smoking and how stopping smoking is probably the best way to improve your health.

Where did the story come from?

The study was carried out by a large collaboration of researchers from around the world, and was funded by the US National Institutes of Health and numerous other cancer research-funding bodies and institutions.

It was published in the peer-reviewed science journal, Nature Genetics.

BBC News reported the story accurately, emphasising that not smoking is the best way to reduce your risk of developing lung cancer (as well as many other cancers).

What kind of research was this?

This was a cross-sectional study looking for genetic traits that may raise the risk of developing lung cancer.

Lung cancer, the researchers state, causes more than one million deaths worldwide each year and is mainly caused by tobacco smoking.

But some studies have indicated there is an underlying genetic component to the risk of developing the life-threatening condition.

This study sought to better understand this link by comparing the genetics of people with and without the disease.

This type of study is a useful first step in identifying potential links between genes and disease, but it cannot prove that a certain gene causes a disease. More biological studies are needed to prove the underlying mechanism by which a gene causes or contributes to disease. 

What did the research involve?

The research compared large groups of people with lung cancer and those without the disease to see how their underlying genetic variation differed. They also wanted to see whether these differences might be related to the risk of getting the disease.

The main analysis compared the genetics of 11,348 people with lung cancer with 15,861 people without. Any differences identified in this group were then validated in a comparison of a further 10,246 people with lung cancer and 38,295 without. In total, 75,750 people fed into the analysis.

Participants were of European ancestry. The two main types of lung cancer (adenocarcinoma and squamous cell carcinoma) were included.

What were the basic results?

The comparisons identified three gene variants associated with lung cancer.

These were:

  • BRCA2 – this leads to a more than doubling of the relative risk for squamous cell carcinoma (odds ratio [OR] 2.47, 95% confidence interval [CI] not reported) and a 47% increase for adenocarcinoma (OR 1.47, 95% CI not reported). This gene is involved in repairing DNA and is known to significantly increase the risk of breast cancer when it does not function correctly.
  • CHEK2 – leading to around a 62% reduction in relative risk (OR 0.38, 95% CI not reported). The CHEK2 gene controls elements of how a cell self-destructs or stops growing when DNA gets damaged.
  • 3q28 – leading to a 13% higher risk of adenocarcinoma only (OR 1.13, 95% CI not reported)

The researchers indicated that the risk of developing lung cancer is approximately doubled for a smoker carrying the BRCA2 variant, which is 2% of the population. This may have implications for identifying high-risk smokers for lung cancer screening.

How did the researchers interpret the results?

The study authors stated that, “These findings provide further evidence for inherited genetic susceptibility to lung cancer and its biological basis.

“Additionally, our analysis demonstrates that imputation can identify rare disease-causing variants with substantive effects on cancer risk from pre-existing genome-wide association study data.”

Conclusion

This study identified new genetic variants linked to the risk of lung cancer in European adults. One of the variations was linked to the BRCA2 gene, which is already known to be associated with a higher risk of developing breast cancer.

The study provided some new evidence of the potential genetic origin of lung cancer, but provided no proof that the genetic variants caused the cancer. However, each of the genetic variants had a plausible biological link to the way in which it might cause cancer.

But cancer often involves the accumulation of genetic damage in many gene regions rather than just one, so identifying these single genetic risks is not the full picture.

In addition to genetic risks, which you can’t change, there are lifestyle risk factors that influence risk, the biggest of which is smoking. If you smoke, you are significantly increasing your risk of developing lung cancer later in life.

It appears that if you also have the BRCA2 gene variant, the risks may be even higher. The study estimated that around 2% of the population are smokers who also carry the BRCA2 variation, but it was unclear how the researchers arrived at this estimate or if this would be similar in the UK population.

The study’s results would be improved by analysing genetic variation in more diverse populations, as the people in this study were described as mainly of European descent.

Professor Peter Johnson, Cancer Research UK’s chief clinician, explained to the BBC that, “We’ve known for two decades that inherited mutations in BRCA2 made people more likely to develop breast and ovarian cancer, but these new findings show a greater risk of lung cancer too, especially for people who smoke.”

As Professor Johnson rightly concludes, “The single most effective way to reduce the risk of lung cancer is to be a non-smoker.”

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

 

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