Smoking and the breast cancer risk gene BRCA2 combine to "enormously" increase the chance of developing lung cancer, a study of 27,000 people has suggested.
The research, published in the journal Nature, found the gene could double the likelihood of getting lung cancer.
And some men and women faced a far greater risk, a team at the Institute of Cancer Research in London said.
Cancer Research UK suggested drugs targeted at breast cancer may work in some lung cancers.
The links between variants of the BRCA genes and breast cancer are well established - a diagnosis led Hollywood actress Angelina Jolie to have a preventative double mastectomy - but it has also been linked with an increased risk of other cancers affecting women such as ovarian cancer and prostate cancer in men.
The study compared the genetic codes of people with and without lung cancer.
Smokers have 40 times the chance of developing lung cancer, but those with a BRCA2 mutation were nearly 80 times more likely, the analysis showed.
A quarter of those carrying the mutation, and who also smoke, will go on to develop lung cancer, the research team said.
"It is a massive increase in the risk of developing lung cancer," said Prof Richard Houlston from the team.
"There is a subset of the population who are at very significant risk.
"The most important thing is reducing smoking; it is so bad for other diseases, as well as [increasing] the risk of lung cancer."
Mutations to the BRCA genes stop DNA from repairing itself effectively.
"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," Prof Houlston added.
The discovery could mean treatments that are being developed for breast cancer may also work in some cases of lung cancer.
"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," said Prof Peter Johnson, Cancer Research UK's chief clinician.
"Importantly this research suggests that treatments designed for breast and ovarian cancer may also be effective in lung cancer, where we urgently need new drugs.
"But, with or without one of these genetic flaws, the single most effective way to reduce the risk of lung cancer is to be a non-smoker."
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