Study of genetic variants in common cancers paves way for targeted screening

BMJ 2013; 346 doi: (Published 27 March 2013) Cite this as: BMJ 2013;346:f1991
  1. Geoff Watts
  1. 1London

Scientists studying the genomes of people with and without three common cancers have identified more than 80 new genetic variants that distinguish the two groups. The scientists, who are based at Cambridge University, London’s Institute of Cancer Research, and elsewhere, believe that their findings will eventually allow screening programmes to be targeted at people most at risk of these cancers.

The study was funded by the Wellcome Trust and Cancer Research UK. It compared DNA from more than 100 000 healthy people with that from another 100 000 people with cancer. A commentary on the work and its implications for public health can be found in Nature Genetics.1

“One of the main drivers of this research has been that the technology has advanced to a point at which you can buy analytical chips relatively cheaply,” said Doug Easton, Cambridge professor of genetic epidemiology. “That’s what’s enabled us to put together an experiment on this scale.”

The researchers found that certain single nucleotide polymorphisms, one category of genetic variants, were more common in people with prostate, breast, or ovarian cancers. The greater the number of variants in a person’s DNA, the greater the risk.

In prostate cancer the researchers found 23 new variants, 16 of which were associated with the more aggressive forms of the disease. They also found 49 new variants in association with breast cancer, a number that more than doubles the known total. The figure for ovarian cancer was 11.

“Results of this type are going to have implications for public health and screening,” said Ros Eeles, professor of oncogenetics at the Institute of Cancer Research.

Taking the example of prostate cancer, she pointed out that screening was currently based on age. “The thing that’s important about these results is that you can now refine the risk profile.” In other words, identify those people most at risk of aggressive as opposed to indolent forms of the disease and target screening tests at them.

The new work was reported in 13 papers published by Nature Genetics and four other journals. One of the studies seems to provide the answer to a question that has puzzled researchers since the discovery of the BRCA1 and 2 genes. Although faults in these genes are known to increase the risk of breast cancer, not all carriers develop the disease.

The new data indicate that possession of the additional variants is what accounts for the difference. Women in the study with a faulty BRCA1 gene and many other genetic variants had a greater than 80% chance of developing breast cancer by the age of 80. By contrast, the risk in women with a BRCA1 fault but only a few of these variants was 50%.

The researchers suggest that a fuller understanding of these variants may point to new treatments. Looking to the more immediate future, Easton said, “It’s clear that beneath the surface a lot more of these markers are waiting to be identified.”


Cite this as: BMJ 2013;346:f1991