Turn me on, turn me off: a new genetic way to tackle cancer?

Diet and supplements can affect the way that inherited diseases are passed from one generation to the next, scientists are discovering

According to textbook genetics the answer is no: the genes you are born with are the ones that your children will inherit, unless there is a rare random mutation. But this is now being challenged by the results of several recent experiments that could have implications for the way we prevent and treat disease.

Take what happened to some laboratory rats at the Centre for Reproductive Biology in Washington State University. Pregnant females were exposed to a fungicide widely used in vineyards just as their foetuses were developing as either males or females. The result, reported in Science, was that the male “pups�?had a low sperm count and low fertility.

This is not so surprising. For some years biologists have known that, far from being fixed sets of instructions, some genes can be affected by factors in the environment, including in the womb. This process, known as epigenetics, doesn’t change the gene itself, just whether it is turned on or off.

But what happened next surprised the scientists. They found that the pups from these rats, which could still father young, suffered from exactly the same problem, as did their “grandchildren�?and their great-grandchildren. We all carry minute traces of synthetic chemicals �?maybe as many as 200 of them �?in our blood. Could some of them be affecting our genes �?and if so, could any harm caused be passed on?

“This is a new way to think about disease,�?says Michael Skinner, the lead researcher, who believes that such inherited epigenetic changes might already be playing a role in breast and prostate cancers. “Their frequency is increasing faster than would be expected from genetic mutations alone,�?he adds.

And if such animal studies are applicable to human beings, it is not just grandmother’s pesticide exposure that could have a long-distance effect, suggests another study on rats reported in The Journal of Physiology. The quality of food that a female gets during pregnancy or while breastfeeding has a direct effect on the risk of her grandchildren developing diabetes. Males and females respond differently: granddaughters are more at risk from a poor diet during pregnancy and grandsons suffer more if their grandmother was undernourished during breast-feeding.

In both these cases outside factors �?toxins and diet �?have affected not the actual sequence of certain genes but the way in which they behave, known technically as their “expression�?

The most dramatic example of this process came in a 2004 study which found that by adding health-store supplements such as folic acid, vitamin B12 and choline to the diet of pregnant mice it was possible to prevent the harmful effects of a gene by turning it off. Usually, these pups would have inherited from their parents a gene called agouti, which would have given them a yellow coat and a raised risk of obesity, diabetes and cancer. The supplement was able to �?silence�?the damaging mutation and the rats were born a normal colour and grew to a normal weight. The lead researcher, Randy Jirtle, Professor of Radiation Oncology at Duke University, North Carolina, says: “It doesn’t mean that these supplements necessarily confer the same benefits on humans. But it shows that supplements can have a dramatic effect on inheritance.�?

Such studies point to a new way of thinking about the complicated links between genes and disease. One big puzzle in this area has been the disappointing results from studies on identical twins who have the same genes but different diseases. Something in the environment is making the difference, but what? According to a study in the Proceedings of the National Academy of Sciences, the answer could well be these epigenetic changes which have been showing up in the animal studies.

To test the possibility, researchers in Europe looked at the way genes were being “silenced�?or “expressed�?in 80 identical twins aged between 3 and 74. They found that when the twins were young the expression of all their genes was virtually identical for each pair, but as they grew older 35 per cent of the pairs showed increasing “epigenetic differences�? They were becoming less alike because factors in the environment were changing the behaviour of their genes.

Professor Tim Spector, a rheumatologist who runs the twin research unit at St Thomas�?Hospital, London, was involved in the trial. He says: “Epigenetics provides a new level of control over genes.�?

Epigenetics may also be important in cancer. For most tumours to grow, genes with anti-cancer activities have to be turned off; it is possible that some epigenetic factor such as pesticides does this. Already a German company, Epigenomics, is developing a test that shows the extent to which genes linked with prostate and breast cancer are turned on or off, which in turn is linked with how malignant the tumour is likely to be.