More Bad News for Smokers

In the two decades since we learned the BRCA2 gene mutation increases breast cancer risk, we've discovered it's also tied to ovarian, prostate, pancreatic, and fallopian cancers as well as melanoma. Now we know it also doubles a smoker's risk for lung cancer.

Researchers discovered this by scanning the genomes of eleven-thousand people of European descent looking for variants that would up their risk for lung cancer. They found mutations of the BRCA2 and CHEK2 gene significantly upped a person's risk and doubled it for smokers.

It makes sense when you understand that BRCA2's normal function is to suppress tumors. It encodes a protein that repairs damaged DNA to maintain the stability of a cell's genetic material. Like other tumor suppressors, BRCA2 prevents damaged cells from growing and dividing uncontrollably. But people with certain variants of BRCA2 produce proteins that do NOT repair DNA damage.

For smokers who have either a BRCA2 or CHEK2 mutation, the risk for lung cancer is 25 percent. Without the mutation, a smoker's risk is far less at 15 percent. Since lung cancer remains the leading cancer in the US, killing both men and women, uncovering BRCA2's role in the disease can add to treatment options.

Doctors could try therapies that are effective in fighting BRCA2 associated breast cancers. One example is a chemotherapy called PARP inhibition. PARP1 is another protein that repairs DNA damage. By inhibiting it, PARP1 would be stopped from repairing damaged cancer cells. This would make lung cancer cells more vulnerable to chemotherapy and radiation, possibly improving a patient's chances of survival.