Testing for a range of genes that raise the risk of cancer will allow scientists to accurately identify people with a high chance of developing the disease, opening the way to personalised strategies for prevention, according to a study in Nature Genetics1.
Screening already exists for a few high-risk genes, such as BRCA1 and BRCA2, but cancers are more often caused by the additive effect of many common genes. Cancer Research UK scientists believe that identifying these genes will bring genetic tests with the power to accurately forecast cancer risk.
They predicted the importance of genetic factors by analysing data from several thousand women with breast cancer. Over 50 per cent of cases are likely to occur in just 12 per cent of women at high genetic risk. Screening these women intensively or treating them with preventative drugs could potentially save many lives.
Working in Cancer Research UK’s laboratories at Cambridge University, scientists analysed the incidence of breast cancer in the relatives of 1,484 women with the disease. They used complex computer models to predict the importance of inheritance in breast cancer risk.
When they plotted the results on a graph, they formed a bell shape – called a normal distribution – suggesting that the inherited risk was caused by lots of genes, each with a modest effect, rather than a small number of high risk genes.
There was a big difference between those at the highest and lowest risk, indicating that testing a woman’s genes can be an effective way of predicting whether or not she is likely to develop the disease. Eighty-eight per cent of cases were found in the 50 per cent of women at highest risk, with 50 per cent likely to occur in the 12 per cent of women at the top end of the scale.
Study author Dr Paul Pharoah of Cancer Research UK’s Human Cancer Genetic Group says: “Our results showed that many common genes seem to add together to raise the risk of breast cancer. In the future, we should be able to test for a selection of these, accurately identifying those women who have a high chance of getting the disease.
“Rather than spending lots of money on a one-fits-all breast screening programme that examines some women too often and others not often enough, we could plan screening according to a woman’s risk. And for women with a very high risk of the disease, drugs like tamoxifen may be useful preventative agents.”
Dr Pharoah and his colleagues believe that genetic testing will be far more effective than current predictions of breast cancer risk, which are based on a woman’s reproductive and family history.
They examined 3,209 cases of breast cancer as part of a population based study that looked at these risk factors, and found that they were much less effective at distinguishing between women at high and low risk. The 50 per cent of women at highest risk accounted for only 62 per cent of breast cancers.
Dr Pharoah adds: “If we’re going to adjust preventative strategies according to a woman’s risk of breast cancer, we have to be reasonably sure about our risk estimates. At the moment, predictions of risk are not very accurate, but as we identify more and more breast cancer genes, that is going to completely change.”
Prof Gordon McVie, Joint Director General of Cancer Research UK, says: “Prevention is one of the key priorities of Cancer Research UK, but to be effective, we need to be able to target ways of preventing cancer at those people whose risk of the disease is highest. This important research shows that by assessing people’s genetic risk, we can start to tailor preventative strategies for the individual.”
Sir Paul Nurse, Joint Director General of Cancer Research UK, says: “A person’s genetic risk of cancer often comes from the cumulative effects of many genes, each of which individually may only have a small effect. We need to identify these small-effect cancer genes in order to understand their contribution to breast cancer and to improve the success of prevention.”
- Nature Genetics30 March 4, 2002
Note to editors:
Cancer Research UK has a long-standing interest in ways of targeting chemoprevention at women with a high risk of breast cancer and is initiating the IBIS-2 trial, to see whether aromotase inhibitors can be effective at reducing the incidence of the disease in these women.