Our professor of clinical genetics, Professor Gareth Evans, is one of the names behind a piece of research that’s highlighted a new mechanism in our genetic make-up that can result in breast cancer.


By looking just outside of the gene at the material surrounding it, we have been able to identify a variant which makes BRCA1 appear that it’s not mutated, when in fact it is. So, families with a strong history and yet who test negatively for BRCA1 and BRCA2 could be carriers of this variant, which is causing their increased risk.


This is the first time researchers have identified that variants outside the gene can result in breast cancer and the mechanism called epigenetic silencing which causes it.


Prof Evans likened the discovery to finally finding an error after looking in the wrong place: “DNA is similar to a book that’s full of chapters. Usually, when we’re trying to find errors in the genetic code, we’re looking for spelling mistakes in the chapters. But this spelling mistake has been found in the spine of the book – it’s not somewhere we’d previously looked and yet, when we’ve investigated this area, we’ve found one of these typos and it’s causing an issue in the pages of the book.”

Prevent Breast Cancer chairman, Lester Barr, added: “What Professor Evans has found is hiding in the piece of DNA which sits beside the gene and was previously thought not to do anything. In fact, we used to call this ‘junk DNA’ a by-product of evolution. But what we now know is that it’s not all junk: this DNA seems to have a modifying effect on the gene.”


He added: “This research could eventually allow us to offer additional screening to those who have a strong family history of breast cancer but do not have the mutated BRCA gene. This could potentially save thousands of women and men from developing genetic breast cancers.”


Currently cancer causing variations in BRCA1 or BRCA2 are identified in around 20% of families with multiple women with early-onset breast and ovarian cancer. Indeed, back in 2013, Angelina Jolie was found to carry a variant in the BRCA1 gene associated with her own increased family risk. However, for many women, the cause of many cases of breast and ovarian cancer in their families remains unknown.


This new research was funded by Prevent Breast Cancer and NIHR and found evidence of the inherited gene variation in two families from Greater Manchester with early-onset breast and ovarian cancer.


Rebekah, 26 from Manchester, has a family history of early-onset breast cancer and is from one of the two families where this new variation has been identified.


She said: “With such a strong family history of breast cancer, I was always aware that I might be at higher risk. When my mum was told she didn’t carry the BRCA mutation but did have this new genetic change, I decided I needed to know my risk too. Knowledge is power, so I wanted to be on the front foot and have a clear understanding of my own risk of getting breast cancer. Thankfully, I tested as negative which means that I don’t have a raised risk. Knowing this has changed my outlook; I’m not going to be spending my life worrying about getting cancer – and any kids I later have won’t be at higher risk, either.”


Researchers are now examining the exact mechanism as to how the variant switches off the BRCA1 gene and whether other variants in this region have a similar effect which will help to determine which women are at highest risk of breast and ovarian cancer.