Whether a smoker gets lung cancer may come down to the effectiveness of a single gene. Researchers in Scotland have found that switching off one gene in laboratory mice allowed the development of cancers in test animals exposed to the chemicals in cigarette smoke.
The gene produces an enzyme, glutathione S-transferase, a powerful substance which breaks down toxic chemicals. Humans also have genes which produce these enzymes. "This is a very exciting finding. It's long been known that our bodies contain factors which determine our sensitivity to cancer- causing chemicals," explained Prof Roland Wolf, who led the team of Scottish scientists from Dundee, Glasgow and Edinburgh.
"Now we've shown for the first time that a single gene could be profoundly important in protecting us against cancer. That's good news, because it's easier to manipulate one gene than many."
The researchers exposed the skin of mice to chemicals which occur in cigarette smoke. Mice which could not produce the enzyme experienced between 3.5 and 10 times as many skin tumours as those which did produce the enzyme, according to the researchers who published their work yesterday in the Proceedings of the National Academy of Sciences.
The work showed that a single gene "can have a profound effect" on tumour formation, according to the PNAS report. It also suggested that the gene and its enzyme "may be an important determinant in cancer susceptibility, particularly in diseases where exposure to poly- cyclic aromatic hydrocarbons is involved, for instance in cigarette smoke-induced lung cancer".
Prof Wolf, of the Imperial Cancer Research Fund's molecular pharmacology unit at Ninewell's Hospital and Medical School, Dundee, said the gene could be one reason why some heavy smokers escaped lung cancer and lived to an old age while others died young.
The hydrocarbon chemicals were thought to play a "pivotal role in human cancers associated with cigarette smoking, such as tumours of the lung and bladder", according to the report. The enzyme was also found to be plentiful in human lung and bladder tissue. There was individual variability in the way the gene produced the enzyme, how- ever, which could alter a person's susceptibility to cancer.
The enzyme itself was not essential for life nor did it appear to support any critical physiological function, according to the researchers. It was particularly effective at detoxifying the particular cancer-causing chemical used in the study, however.
Additional reporting by PA
