DNA discovery points to new clinical biomarker in predicting breast cancer risk

Scientists have identified a new biomarker in the blood that could help identify more women at an increased risk of breast cancer.

Such women might benefit from risk-reducing measures.

In a prospective study, researchers from Imperial College London and the Human Genetics Foundation (HuGeF) in Torino, Italy, have concluded that DNA methylation levels in blood cells are associated with breast cancer risk, and could be used to identify women at increased risk of developing the disease.

DNA methylation is the process by which methyl groups are added to the DNA, modifying its function and regulating how much of a gene's protein product gets made, something that is essential for normal cell development. The team’s findings build on a growing body of evidence suggesting that lower than normal methylation of white blood cell DNA could be predictive of a heightened breast cancer risk.

The studies analysed by the researchers took blood samples from healthy women who were then monitored for an average period of around nine years. The women who developed breast cancer during this time had a lower level of DNA methylation in their white blood cells, compared to the women who didn’t develop the disease.

The research highlights DNA methylation as a key player in our understanding of breast cancer risk – adding to a growing list of known genetic variants associated with an increased risk of the disease – which will ultimately help us refine and improve the ways we assess, and monitor, an individual’s breast cancer risk.

Whilst this research is at a very early stage, it is hoped that one day scientists could potentially be able to proactively change methylation patterns, underlining the importance of research into epigenetics.

Further studies will now be required to understand why the methylation patterns observed in blood cell DNA are linked to breast cancer risk, as this is not currently known. It is hoped that women already known to be at increased risk of developing the disease could be given a blood test to assess and monitor methylation levels in order to better understand their risk and inform decisions around preventative treatments.

The international study saw researchers analyse blood from around 2,600 women from four cohorts: Breast Cancer Now's Generations Study, the European Prospective Investigation into Cancer and Nutrition, Italy, the Norwegian Women and Cancer (NOWAC) study and the Melbourne Collaborative Cohort Study.

Notably, while three of the four cohorts confirmed this finding, the association was not replicated in the NOWAC study, something that poses questions about potential differences between populations.

Dr James Flanagan, from the Department of Surgery and Cancer at Imperial College London, said: “This study shows the importance of investigating the epigenetics of breast cancer risk and of continuing to fund research in this particular area.

“This novel and exciting topic has the potential to show how lifestyle and environmental factors influence one’s risk of developing breast cancer. Crucially, epigenetic patterns are modifiable, meaning that, unlike genetic risk, there is a possibility that we may find ways in which you can modify your epigenetic risk, so that fewer people develop cancer in the first place.”

Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now, which part-funded the study, said: “This study represents a really important brush-stroke in the bigger picture of breast cancer risk and prevention. Further research will now be required to understand why this loss of methylation might increase a woman’s risk of breast cancer, the findings of which could provide crucial insight into how breast cancer develops and how to prevent it.

“The ultimate goal of The Generations Study is to build accurate and comprehensive models to calculate breast cancer risk, as, if we can predict who might get breast cancer, we can intervene to reduce their risk of developing the disease. As such, we are very proud to have supported this research and we look forward to further studies in the fascinating field of epigenetics.”

The research, which has been published in Clinical Epigenetics, was funded predominantly by HuGeF (Torino, Italy), the Australian National Health and Medical Research Council, the Cancer Council Victoria (Melbourne, Australia), Breast Cancer Now, Cancer Research UK, The Institute of Cancer Research, London and the Imperial College Biomedical Research Centre.

Adapted from a press release issued by Breast Cancer Now.