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They doubt that these genes will be easy to find, that they are especially important, or that finding them would make a lot of difference to cancer treatments. They compare the effort to “the search for the end of the rainbow”.
Ever since the human genome was sequenced, enthusiasts have claimed that it holds the key to explaining many diseases, including cancer.
But writing in the British Medical Journal, Stuart Baker, of the US National Cancer Institute in Bethesda, Maryland, and Jaakko Kaprio, a genetic epidemiologist from the University of Helsinki, said that the chances of finding simple genetic changes that predispose to cancer are low.
“Huge resources are being invested in the search for common inherited genetic variants that increase susceptibility to cancer,” they said. But there is only “a small chance” that they even exist. Researchers believe that if they can identify one or perhaps a few genes that make a big difference to the risk of cancer, people carrying them can be counselled, or given preventive treatment.
The classic examples are the BRCA1 and 2 genes, which affect the risk of breast cancer; carrying one of these genes greatly increases the lifetime risk of the disease. Some women have had their breasts removed after being identified as carriers. But finding many more examples and proving any benefit from such discoveries needs careful analysis, the two specialists said. Such studies are expensive because they need large sample sizes.
A US project, the Cancer Genetic Markers of Susceptibility, plans to spend $14 million (£7.9 million) looking for genetic changes that make people more likely to get prostate or breast cancer. However, the specialists argued that there may be three reasons why such research might fail. For cancer to develop, the tumour cells need to grow more quickly than is normal, a change that is likely to involve alterations in many genes, not just a few.
A second reason is that when people migrate, they quickly adopt the same cancer patterns as the native population. Within one or two generations, far too soon for any genetic change, they suffer cancers of the same sort, and to the same degree, as the locals. That suggests that environmental changes, such as diet, are much more important than genes.
A final reason can be found in studies into twins. Identical twins share all the same genes, while non-identical twins do not. That means that if genes were all-important, identical twins would be much more likely to suffer the same cancers than would non-identical twins. Studies of a Norwegian twin database do not suggest that this is the case: genes make only a “small to moderate” contribution to the risk.
The authors calculated on the basis of these results that only 9 to 22 per cent of prostate cancers would be found in people with susceptible genes, 8 to 14 per cent of breast cancers, and 5 to 13 per cent of bowel cancers.
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