Smoking and cancer link proved at last

American scientists have finally shown how tobacco smoke causes the changes that trigger lung cancer in human cells, providing what Professor Gordon McVie, of Britain's Cancer Research Campaign, yesterday called "the last nail in the coffin for the tobacco companies' denials".

The new finding is expected to lend ammunition to plaintiffs who are bringing lawsuits against the US tobacco industry, and to lawyers preparing to serve writs on British tobacco companies, alleging that they helped cause 40 people to develop lung cancer.

The industry itself was quick to deny that the results, published in the latest edition of the prestigious US journal Science, will have any effect on the many class-action suits now in progress against them. They also called the results of the work "preliminary, rather than conclusive".

The cancer research community, however, takes a different view. The new research builds on decades of work to show that a cell gene necessary to stop cancer, called p53, is damaged by a component of tobacco smoke known as BPDE (see panel).

The study, carried out jointly by teams at the Beckman Research Institute in Duarte, California, and the University of Texas, "provides a direct link between a defined cigarette smoke carcinogen and human cancer mutations," write the authors.

Previously, the strongest evidence connecting lung cancer and smoking came from statistical studies. The landmark research began in 1951, led by the Sir Richard Doll, who studied 34,000 British male doctors. His work, now regarded as a classic piece of scientific investigation, showed that people who smoked were significantly more likely to develop lung cancer.

But tobacco companies have argued for decades that growing numbers do not constitute proof, and pointed to people who do not smoke but develop lung cancer, and those who do smoke but do not become ill.

Professor McVie was jubilant yesterday. "We have known ever since p53 was discovered that it was abnormal in 95 per cent of lung cancer cases... Before this, the level of debate with the tobacco companies has been for us to present the epidemiological evidence, and them to say 'So what?' " Now there was "incontrovertible evidence" that "tobacco smoke has a devastating and crippling effect on cells".

American tobacco companies said this weekend that the findings would not have any effect on their existing legal and regulatory battles. Philip Morris, which produces Marlboro, said that "this research does not change the fact that smoking is an informed choice that people have made, and we believe will continue to want to make." It added that the research was "consistent with our long-held position that the mechanism by which a cell becomes cancerous is a complex process not yet explained".

Brown and Williamson noted that "BPDE is everywhere... It is in air, soil and produced by the combustion of any kind of organic matter [such as] back yard barbecues and the exhaust of automobiles and trucks." The levels of BPDE in tobacco smoke are too low to cause cancer in laboratory animals, it said.

The denials did not stop their shares falling. On Friday Philip Morris ended down 5 per cent, as did British American Tobacco Industries, while RJR Nabisco (Camel) was 3 per cent lower.

Anti-smoking lobbyists were delighted. Ash said the discovery could make it harder for companies to sell their products in Third World countries - currently a number one target: "They now have a moral, if not legal, duty to warn their customers that their products can cause lung cancer."

Proof of a definite link between smoking and reduced human defences against the onset of cancer will also increase pressure on the Government to introduce bans on advertising and on smoking in public places.

The evidence

The new research looked at the effects of a single component of tobacco smoke, known to cause cancer - BPDE - on a cell gene called p53, writes Charles Arthur.

Its function is to guard against cells mutating and multiplying out of control. Normally if that happens, the level of the p53 protein inside the cell rises, triggering it to commit suicide by a process called "apoptosis".

Cancer occurs if the p53 gene fails. Each gene consists of hundreds of "codons", or DNA instructions. A mutation in any codon may make the gene ineffective. Such alterations can happen accidentally, by exposure to ultraviolet light - as in skin cancer - or to other carcinogens. The faulty p53 gene can't trigger apoptosis. The result: malignant cancer.

The latest research treated human cells with benzo[a] pyrene diol epoxide - BPDE. The researchers then examined the mutations in the p53 gene, and found that the position of the affected codons matched exactly with those which are most common in lung cancer victims. The conclusion: tobacco smoke causes lung cancer, and this is how.