Scientists have for the first time pinpointed a protein that explains how smoking can directly lead to genetic changes that cause cancer – research published today (Tuesday) 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.”


For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.


* Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. Hays et al. 2008. British Journal of Cancer.

Lung cancer

Lung cancer is the second most common form of cancer in the UK after breast cancer. Smoking and passive smoking cause nine out of ten lung cancers.

There are over 38,300 new cases of lung cancer in the UK each year. Each year more than 33,000 people die from the disease.

Lung cancer is the most common cancer in the world with 1.3 million people diagnosed every year. Worldwide, the highest rates of lung cancer in men are currently in the regions of Central and Eastern Europe, and for women in Northern America.

Smoking and risk of lung cancer

Smoking is the single biggest preventable cause of cancer in the world. It is responsible for nine out of ten cases of lung cancer in the UK, with smokers overall 26 times more likely than non-smokers to develop the disease.

Half of all smokers eventually die from lung cancer or another smoking-related illness. And a quarter of smokers die in middle age – between 35 and 69.

The good news is that most of these deaths are preventable by giving up smoking in time.

The best way to reduce the risk of cancer is to give up smoking completely.

British Journal of Cancer

The BJC is owned by Cancer Research UK and its mission is to encourage communication of the very best cancer research from laboratories and clinics in all countries. Broad coverage, its editorial independence and consistent high standards have made BJC one of the world’s premier general cancer journals. Visit the BJC homepage.

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