Scientists unravel how smoking causes cancer

May 15 2008

Scientists have for the first time pinpointed a protein that explains how smoking can directly lead to genetic changes that cause cancer - research published in the British Journal of Cancer reveals.

Researchers have now discovered that the production of a protein called FANCD2 is slowed when lung cells are exposed to cigarette smoke. Low levels of FANCD2 leads to DNA damage, triggering cancer.

These findings add to the vast body of evidence linking smoking to lung cancer and may help scientists improve treatments for the disease in the future.

Cigarette smoke curbs the production of 'caretaker' proteins, like FANCD2, which normally prevent cancer by fixing damages in DNA and causing faulty cells to commit suicide.

Lead author, Dr. Laura Hays, Research Assistant Professor in the Department of Medicine and member of the Cancer Institute at Oregon Health & Science University in the US said: "These findings show the important role FANCD2 plays in protecting lung cells against cigarette smoke and may explain why cigarette smoke is so toxic to these cells."

Senior author, Dr. Grover Bagby, Founding Director of the Oregon Health & Science University Cancer Institute and Professor at the Northwest Cancer VA Research Center at the Portland VA Medical Center, added: "Dr. Hays' work shows that FANCD2 is an important protein in protecting against cancer, and cigarette smoke knocks out its production.

"Although there are probably other proteins involved in this process, we know this is a key one because cells with very high levels of FANCD2 were resistant to the toxic effects of the smoke."

The authors created an artificial windpipe in the lab to replicate the environment of a smoker's lung. They then studied the effects of cigarette smoke on different proteins in cells and found that FANCD2 levels were low enough to allow DNA damage.

FANCD2 is part of a family of proteins involved in an inherited condition called Fanconi anaemia. People with the condition are more likely to develop cancers at a young age and have low levels of these proteins.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: "This interesting piece of science adds to our understanding of why smoking is so deadly. Smoking is the single biggest preventable cause of cancer and causes nine out of ten cases of lung cancer.

"But the good news is that quitting works - after five years without smoking your risk of a heart attack will have fallen to half that of a smoker. And after ten years your risk of lung cancer will have halved too.

"We know that giving up is tough but smokers are four times more likely to quit successfully with NHS support and stop smoking medicines such as nicotine gum or patches to manage cravings."