From John Snow’s early investigations into cholera, Pasteur’s experiments and Koch’s postulates, we have been able to work out that germs are the root cause of many diseases.  These findings quickly led to the development of preventative interventions to help reduce the incidence of these diseases in a population. As an example, our understanding of the causes of disease and the development of successful vaccines has eradicated smallpox from the planet – a disease estimated to be responsible for 300-500 million deaths during the 20th century.

Breast cancer should be no different.  The key to preventing the disease is understanding the causes.  However, unlike smallpox, the causes of breast cancer are a complex mixture of genetic, lifestyle and environmental factors. And to complicate matters further, these factors interact with each other to produce a chaotic web of risk factors, which impact different people in different ways.

Studies that look into the causes of a disease in a population are called epidemiology studies. The bigger they are, the more accurate the results are likely to be. Pooling data from similar studies is a great way to achieve this and the COGS project (Collaborative Oncological Gene-Environment Study) is a model example of how large-scale collaborations can lead to dramatic advances in research.

Cancer prevention

COGS is an EU-funded project bringing together four large consortia investigating genetic risk factors for breast, ovarian and prostate cancer. The consortium behind the genetic epidemiology of breast cancer is called the Breast Cancer Association Consortium (BCAC) and includes over 80 studies from all over the world, including the Breakthrough Generations Study, the largest and most comprehensive study into the causes of breast cancer in the world. “This study is crucial because we are now aware that breast cancer is influenced by a number of factors,” said Dr Nick Orr, Group Leader of the Generations Study. “Studies such as the Generations Study and large collaborative efforts such as BCAC will ultimately give us some answers as to why women develop breast cancer and what we can do to prevent it in the future.”

The BCAC are trying to identify new genetic variants, or tiny changes to the genetic code, which influence breast cancer risk. By investigating these variants in fine detail it is possible to work out not only which genes are affected by these changes, but also what the impact these changes have on the function of a particular gene.

Risk factor interactions

The BCAC and COGS have so far published some amazing findings including the identification of 41 new genetic markers associated with breast cancer risk, 4 genetic risk markers specifically associated with ER-negative disease and specific risk-raising variants associated with BRCA-mutant breast cancer.

But we know that the causes of breast cancer are more than just genetic. In a landmark study published in 2013, the COGS project provided the first strong evidence to show that the level of breast cancer risk associated with some of these genetic variants was altered by known environmental risk factors such as alcohol consumption and the number of births had by the mother.

This ability to combine genetic, environmental and lifestyle factors into a model which accounts for their interactions is how we, in the future, hope to be able to reduce the number of breast cancer cases. As we gather more knowledge of breast cancer risk factors and devise cleverer ways to analyse them, we can move towards producing accurate tests to predict an individual’s risk. Identifying those at high-risk of breast cancer means that we can then target preventative interventions to the right people, ultimately reducing the number of women and men affected by breast cancer.

Dr Matthew Lam is Breakthrough Breast Cancer’s Senior Research Officer