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March 31, 2008

Genetic variants may be ‘trading’ one illness with another using new genes, Oxford research shows

A genetic trade-off between type 2 diabetes and prostate cancer has been identified by scientists, with the discovery of genes that can raise the risk of one condition while protecting against the other.

The research suggests that the two very different diseases may be influenced by the same biological pathway, with people’s risk rising or falling according to particular genetic variants they inherit. 

These insights will improve understanding of both the adult-onset form of diabetes and prostate tumours, and perhaps other cancers as well. This promises the development of new therapies, and should help scientists to avoid designing drugs aimed at one disorder that inadvertently trigger the other.

The genetic trade-off has emerged from a major international search for genetic influences on type 2 diabetes, which has linked six new genes to the condition.

One of these is a gene called JAZF1: people who carry one copy of a particular variant are about 15 per cent more likely than usual to develop diabetes, while those with two copies have a 30 per cent increased risk.

A different variant of JAZF1, however, is also known to raise the risk of prostate cancer in men who have it. Research indicates that a raised risk of one disorder is probably balanced by a lower risk of the other.

The findings are especially significant because another gene that has opposing effects on the two diseases, called TCF2, was identified last year by an Icelandic team. A third gene, CDKN2A, appears to raise the risk of type 2 diabetes when over-active, while raising the risk of cancer, particularly malignant melanoma, when under-active.

Mark McCarthy, Professor of Diabetes at the University of Oxford and a leader of the JAZF1 study, said that while one “see-saw” gene could be a fluke, the discovery of three makes it more probable that there is a genuine interaction.

“If you have one version of a gene, you have an elevated risk of diabetes, if you have another, you have an increased risk of prostate cancer,” he said. “It was an entirely unexpected finding when the link first emerged last year, and now we have found it again in a completely different gene.

“It is interesting from a biological point of view, but it might also be important for drug design. It might tell you something about the collateral damage you might do with a drug that targets one condition or the other.”

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