Scientists from Imperial College London say that women with very high levels of methylation in an area of a gene, known as ATM, had double the risk of going on to develop breast cancer, compared to those without the faulty gene.

Their study, which has been published in the journal Cancer Research, found that a woman’s risk of breast cancer may be decided several years before the disease develops.

Dr James Flanagan say he has uncovered compelling evidence that “epigenetic” gene changes may be linked with breast cancer risk.

Flanagan and team examined 640 women with breast cancer and 741 women without (controls) who enrolled in the previous three months. The earliest enrollee joined in 1992. Women donated blood samples every three years before their breast cancer was diagnosed. The aim was to determine whether methylation could predict future cancer risk in women. Methylation is a process by which a single gene undergoes alteration.

Those with the highest level of methylation in a gene area called ATM were found to have double the risk of developing breast cancer later on, compared to women with the lowest levels. The link to subsequent breast cancer risk was more evident among women aged under 60 years.

This is the first study to examine blood at least three years before a cancer diagnosis was made – in the cases of some participants, blood had been sampled eleven years beforehand. This study shows, because of this, that it is not the active cancer in the body or cancer treatment that necessarily alter the genes.

The scientists believe that blood tests could be devised which focus on methylation in single genes to assess breast cancer risk. The test could be used alongside other tools, such as risk-factor profiling and genetic testing.

The authors emphasized that their test now needs to be confirmed with rigorous testing in a much larger number of participants and a wider gene range profiled – just one gene is not enough.

Epigenetics is altering the way researchers think about genes and how they develop. The authors believe epigenetics could eventually play a vital role in preventing cancer.

Experts used to think that cancer risk, when talking about genes, had to be in the fundamental genetic data from our DNA. We now know that chemical modifications to DNA, which control our genes, might play an even greater role that DNA alone in determining how our cells grow.

Dr Flanagan explained:

“We know that genetic variation contributes to a person’s risk of disease. With this new study we can now also say that epigenetic variation, or differences in how genes are modified, also has a role.

We hope that this research is just the beginning of our understanding about the epigenetic component of breast cancer risk and in the coming years we hope to find many more examples of genes that contribute to a person’s risk. The challenge will be how to incorporate all of this new information into the computer models that are currently used for individual risk prediction.

So far we have found alterations in one small region of a gene that appear to associate with risk of disease and so the next step with this epigenetic research is a genome wide approach to try and find all the associated genes.”

Baroness Delyth Morgan, Chief Executive of Breast Cancer Campaign said:

“Dr Flanagan’s research into epigenetics is so exciting because it suggests that there is every possibility that the risk of developing breast cancer could be decided many decades in advance. By piecing together how this happens, we can look at ways of preventing the disease and detecting it earlier to give people the best possible chance of survival.”

In an Abstract in the journal, Cancer Research, the authors concluded:

“Together, our findings indicate that WBC DNA methylation levels at ATM could be a marker of breast cancer risk and further support the pursuit of epigenome-wide association studies of peripheral blood DNA methylation.”

Written by Christian Nordqvist