Breast cancer gene raises lung cancer risk in smokers

Smokers are
more likely to develop lung cancer if they carry a defective version of a gene
associated with breast cancer, a study has found.

Mutations
in the BRCA2 gene have long been linked to increased risk of developing breast,ovarian and prostate cancers. Now, researchers have found that that a specific variant of the gene also increases the risk of lung cancer, particularly in smokers. Lifetime
risk for developing lung cancer for smokers, normally at around 13 percent, rises
to 25 percent for those that possess the defective gene.

This
means that smokers with this mutant BRCA2 have a one in four chance of developing
cancer — almost double the risk of those who don't smoke. The mutant gene is
present in about two percent of the population, so given that there are 10
million adult smokers in the UK, the researchers estimate that up to 200,000
people could be affected.

'Our
study showed that mutations to [BRCA2] have a very large effect on lung cancer
risk in the context of smoking', said Professor Richard Houlston from the Institute
of Cancer Research in the UK, one of the lead researchers. 'Some smokers with
BRCA2 mutations are at an enormous risk of lung cancer — somewhere in the
region of 25 percent over their lifetime', he added.

In the study, published in Nature
Genetics, the researchers compared the DNA of over
11,000 lung cancer patients with that of almost 16,000 healthy controls, all of
European ancestry, and looked for differences between the two groups. They
found that the variant of BRCA2 known as c.9976T was more common in the
patients with lung cancer than without, particularly in squamous cell lung
cancer, the most common lung cancer type.

It is
thought that mutant BRCA2 can no longer properly repair damaged DNA caused by
smoking. 'In the context of smoking there is such an enormous amount of DNA
damage that any loss of DNA repair is going to be an issue', Professor Houlston told BBC News.

Specific drugs for breast or ovarian cancer patients with BRCA2 mutations are
in development and have already shown promising results in clinical trials.
This raises the possibility that these drugs, called PARP
inhibitors, may also work in lung cancer patients with mutant BRCA2. However,
this is only speculative, as whether the drugs will actually work against lung
cancer is not known.

This
study confirms that there is an inherited genetic susceptibility to lung
cancer. Professor Paul Workman, from the Institute of Cancer Research, said: 'All
smokers are taking a considerable risk with their health, regardless of their genetic
profile, but the odds are stacked even more heavily against those with this
genetic defect who smoke'.