We’ve blogged before about the discovery of new prostate cancer genes. And indeed, gene-hunting is such an exciting and busy area of science that it’s likely to feature in the news more and more often. But what, you may wonder, is the point of these studies?

It’s common knowledge that a person’s risk of cancer is affected by the genes they inherit.. But it’s becoming increasingly clear that our genes also affect the way we react to things in our environment like tobacco or alcohol. The big idea is that knowing how these genes work together, and which particular genes a person carries, will allow doctors to personalise prevention advice, screening and treatment options.

This era of personalised medicine is still a while away but the first steps towards it could be taken very soon. Paul Pharoah, one of our scientists at the University of Cambridge, has suggested how our expanding knowledge of breast cancer genes could be used in practical ways to improve early diagnosis for women at high risk of the disease.

High-risk vs low-risk

At the moment, we know about a few “high-risk” breast cancer genes, such as BRCA1 and BRCA2. Inheriting a faulty version of one of these massively increases a person’s risk of developing breast cancer, as well as a few other types. But they’re rare in the general population and are only involved in about 2-5 per cent of all breast cancer cases.

More recently, Cancer Research UK scientists announced that they were homing in on several “medium-risk” breast cancer genes. Individually, these have a much smaller impact on a person’s chances of developing cancer, but together, their effects start to stack up. They’re also a lot more common than the high-risk genes and account for a larger percentage of breast cancer cases.

For example, the ‘risky’ version of the medium-risk FGFR2 gene only increases the risk of breast cancer by a quarter. By comparison, faulty BRCA genes can increase the risk of breast cancer by 3-7 times. However, the BRCA faults are rare, while the ‘risky’ version of FGFR2 is found in 38 per cent of the UK population.

Dr Pharaoh’s analysis, published in the prestigious New England Journal of Medicine, looks at seven of these medium-risk genes. Each one has “risky” version that can increase the risk of breast cancer and a “non-risky” version that does not. His findings include:

  • If a woman has all the non-risky versions (which very few do), their odds of getting breast cancer at some point in their life is 4 per cent or 1 in 25.
  • The average lifetime risk for breast cancer in the UK is 9.4 per cent or 1 in 11.
  • If a woman has all the risky versions (which even fewer do), their lifetime risk is 23 per cent or about 1 in 4.
  • This means that women with all seven risky variants are 6 times more likely to get breast cancer than women with all seven non-risky variants.

Screening by risk

These seven genes alone aren’t going to provide us with enough information to tell individual women about their personal risk of breast cancer – there are too many other factors involved, both known and unknown. But there are areas where we can use what we already know while new genes are being discovered.

The national breast screening programme is one of these. Women are currently invited for screening based on their age, with invitations going out to women aged 50-70. However, they could potentially be screened according to their risk of breast cancer, as determined by their genes.

For example, women younger than 50 with a high genetic risk could be offered screening, while there would be less cause to invite older women with low genetic risks.

This strategy would make the screening programme more efficient. It would mean that women would be offered a personalised screening programme, where their starting age would vary based on the genes that they carry. It would also mean that women who have naturally low risks don’t have to go through the stress of waiting for their results.

Dr Pharoah argues that the cost of providing individual genetic tests would be smaller than the costs of the current broad-brush approach to screening.

Other considerations

And that’s just a first step. Our risk of cancer is influenced by a combination of our genes, our environment and our lifestyle choices. Understanding how our genes and our lifestyle choices interact to affect our risk of breast cancer will also be important in working out which women have the highest risk of the disease.

The current breast screening technique – mammography – is much less effective at detecting breast cancer in younger women than in older women. This is why only women aged 50 or over are currently invited for screening. It also means that if we are to start screening younger women with a high genetic risk of breast cancer, we will need to rely on different methods.

Magnetic resonance imaging, or MRI, is one such technique. Cancer Research UK is funding a trial to see if it could help to detect breast cancer in young women with a high genetic risk of the disease. The technique is very expensive, so it would be best if it was only used in women are revealed to have a higher risk than normal via genetic profiling.

So clearly, there’s a fair bit of work to be done before people can be screened properly according to their natural risk of cancer. We need to know how genes interact with lifestyle factors and we need technology that actually works in younger women. Most of all, the right infrastructure needs to be put in place for accurate genetic tests on a large scale.

But it’s important to realise that these exciting prospects are only on the horizon because of a continuing intensive research effort, aimed at identifying new cancer genes.


Reference: Polygenes, Risk Prediction, and Targeted Prevention of Breast Cancer (2008), Paul Pharoah et al, New England Journal of Medicine 358: 2447-59.