BRCA2 Mutation and Lung Cancer

Defects in the BRCA2 gene may indicate more than just a higher risk of breast and ovarian cancer. A new study shows that about one quarter of smokers who have a defect in their BRCA2 gene will develop lung cancer at some point during their lives.

The link between a BRCA2 gene defect and lung cancer affects about 2 percent of the population, according to the study, published in Nature Genetics.

A defective BRCA2 gene can increase a person’s risk for developing lung cancer by about 1.8 times.

“Smokers in general have nearly a 15 percent chance of developing lung cancer, far higher than in non-smokers. Our results show that some smokers with BRCA2 mutations are at an enormous risk of lung cancer—somewhere in the region of 25 percent over their lifetime,” said Richard Houlston, a professor at the Institute of Cancer Research in London.

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Genes Link Smoking to Disease

As a group, smokers have a 13 percent risk of getting lung cancer—16 percent of male smokers and 9.5 of female smokers will get the disease. This new study indicates that one in four smokers who have the BRCA2 mutation, regardless of gender, may develop lung cancer.

In patients with squamous cell lung cancer (the most common type), the link between lung cancer and the defective gene was strongest. The scientists also discovered a link between squamous cell lung cancer and the CHEK2 gene, which normally prevents cells from dividing when they have suffered damage to their DNA.

A team at the Institute of Cancer Research compared the DNA of 11,348 Europeans who had lung cancer to the DNA of 15,861 people who did not have the disease. The U.S. National Institutes of Health (NIH) and Cancer Research UK funded the study.

When caring for patients with squamous cell lung cancer, it may be wise to give them drugs that are effective against cancers caused by BRCA mutations. Researchers aren’t sure if those patients might benefit from PARP inhibitors, which have been proven effective in treating ovarian and breast cancer patients with BRCA mutations.

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Lung Cancer Is Deadly

"Lung cancer claims more than a million lives a year worldwide and is by far the biggest cancer killer in the UK," Houlston said. "We know that the single biggest thing we can do to reduce death rates is to persuade people not to smoke, and our new findings make plain that this is even more critical in people with an underlying genetic risk."

Dr. David P. Carbone, director of the James Thoracic Center at Ohio State University’s Wexner Medical Center, said the findings are important for monitoring people who have inherited the mutation and targeting treatments to them specifically.

“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,” said Paul Workman, the deputy chief executive of the Institute of Cancer Research. He added that lung cancer is "almost invariably fatal."

Dr. Maurie Markman, an oncologist with the Cancer Treatment Centers of America, said it is fascinating that the same molecular abnormality relevant in breast and ovarian cancers may be linked to an increased risk of lung cancer.

“If confirmed, one can make a very strong statement to anyone known to have a mutation in this gene that if they smoke they absolutely must stop based on an extremely high risk for the development of lung cancer, a malignancy with an anticipated very poor outcome,” Markman said.

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