Huge resources are being invested in the search for common inherited genetic variants that increase susceptibility to cancer. One US project, for example, will cost $14m. But devoting a large research effort to searching for common cancer susceptibility genes has several problems, write authors Stuart Baker and Jaakko Kaprio.

The first is that recent research suggests these genes are unlikely to exist or, if they do, are unlikely to have much of an effect on the incidence of cancer.

A second reason to play down the role of common susceptibility genes is studies suggesting that environmental, dietary, or lifestyle changes have a large effect on the incidence of cancer. These studies show changes in incidence within one or two generations, which is probably too quick to be related to the introduction of new genes.

A final reason to be sceptical comes from results from a study of cancers in twins. By analysing data from identical and non-identical twins, the authors showed that genetic susceptibility made only a small to moderate contribution to the incidence of cancer.

Studies that have shown links between common genes and cancer may be due to bias.

But, even if susceptibility genes were identified, showing clinical benefit would still be difficult, and further large trials would be needed, they add.

"The search for common cancer susceptibility genes faces important methodological and practical challenges for cancer prevention, given the small chance that such genetic variants exist and the difficulty and expense of proving substantial clinical benefit if they do exist," they conclude. "Enthusiasm for this new field of research should not precipitate unwarranted expectations."

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Contact: Emma Dickinson
edickinson@bmj.com
44-020-738-36529
BMJ-British Medical Journal
11-May-2006