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On average, with breast cancer every day. It’s the most common cancer affecting Australian women, with family history, or inheriting a fault in a breast cancer gene, being major risk factors.

And yet gene mutations known to increase cancer risk—such as BRCA1 and BRCA2—are only identified in approximately 20 per cent of women who are offered genetic testing for familial breast cancer. Most women who undergo such testing (typically when there is a known family history of disease) never find an explanation, genetic or otherwise, for their breast cancer predisposition.

Now, research led by the University of Melbourne has identified heritable non-genetic markers for susceptibility to breast cancer: things that can be passed down through the family, but that are not faults in the genetic code of genes.

But wait: if it’s not in your genes, how can it be inherited?

To understand how something can be heritable (capable of being passed down from a parent to a child) but not genetic (a part of your DNA sequence), we need to have a basic understanding of epigenetics: all the things that control how the information stored in your DNA ends up being used by your body.

Think of your DNA as being the complete set of blueprints for building ‘you’, outlining how your body should be constructed and how it should work. A gene is a specific part of your DNA that builds a protein—a page or section that’s part of the bigger blueprint.

However, a blueprint cannot do the building; it needs someone who can interpret it correctly and direct the construction process. This is where epigenetics comes in.

What is epigenetics?

Epigenetics (literally ‘on top of genetics’) refers to the extra layer of information, or the 'instruction manual', that lies above the blueprints of your genes. Epigenetics makes sure that the information about how to build your eye isn’t being used to try and build your leg, even though every cell in your body essentially contains the same complete set of information. It does this by turning certain genes ‘on’ or ‘off’ depending on the situation.

There are several different ways of recording information for the instruction manual in the blueprints themselves, one of which is DNA methylation. DNA methylation refers to the ‘adding on’ of extra bits (methyl groups) attached to the DNA that help regulate whether a gene is turned on or off. It’s a bit like sticking a Post-It note onto a section of the blueprint, saying ‘skip this bit’. The blueprint itself remains unchanged, but the instructions have been modified.

Together, your genetic sequence (the blueprint) plus your epigenetics (the instruction manual for interpreting the blueprint) make up your genome.

What does epigenetics have to do with breast cancer risk?

In the University of Melbourne study, researchers studied how DNA methylation affects breast cancer risk by studying DNA from blood samples of 210 people, all from 25 families with a strong family history of breast cancer.

They identified 24 instances of DNA methylation that can be passed from one family member to another—23 of these instances did not involve changes to the underlying DNA sequence. Often, methylation would occur in a place that affected a cell’s ability to suppress tumour growth.

It’s the first time scientists have taken a systematic approach to scanning the genome in an effort to find places where DNA methylation is heritable, and then applied this to familial breast cancer.

The findings, published in , mean it will become easier for doctors to screen at-risk women and predict their breast cancer risk more accurately. It also opens the door towards developing epigenetics-based treatments for breast cancer patients.