BRCA1 breast cancer research

 

Cancer Focus NI is funding a vital research project led by Dr Kienan Savage at Queen’s University Belfast. The primary focus of Dr Savage’s research is preventing breast and ovarian cancers by investigating how damaged genes – those that can cause cancer – can be repaired.

Dr Kienan Savage

 

Latest cancer research news for high risk women

 

Dr Savage recently identified a number of new cancer genes that appear to be involved in the development of breast and ovarian cancers and some forms of leukaemia.

“These cancers often arise due to damage to genes within our DNA, known as ‘gatekeeper genes’, which control how often cells divide, allowing cells to grow out of control forming a tumour,” he said.

“The new cancer genes that have been discovered appear to play a role in repairing damage to DNA and thereby aid the repair of damaged ‘gatekeeper genes’, helping to prevent cancer.

“My research will add significantly to our understanding of how these genes work to prevent the development of cancer. It may also lead to the development of new quick and effective tests to help decide which treatments specific cancer patients will benefit from, and may identify new proteins that could be targeted for future therapies.

 

Research papers

 

Dr Savage has published two collaborative research papers focusing on the BRCA1 gene and how it can help to reduce breast and ovarian cancer risk.

 

  1. BRCA1 Deficiency Exacerbates Estrogen Induced DNA Change

Dr Savage explains that women with a BRCA1 gene mutation have a very high risk of developing breast and ovarian cancers (up to 85% risk of breast cancer and up to 40% risk of ovarian cancer in their lifetime).

The BRCA1 gene functions within all cells of our body to fix damaged DNA, and thereby prevents damage to genes that control cell growth and protect our cells from becoming cancerous.

All women have two normal copies of the BRCA1 gene but it’s the single mutated copy of BRCA1 (called a heterozygous mutation) that predisposes these women to the high risk of breast and ovarian cancer.

Christine Garrett and Kienan in the lab

 

Shedding light

Because of its important function in all cells of the body, scientists have long asked why do women who carry a mutation in BRCA1 specifically develop breast and ovarian cancers.

This study, led by scientists at Queen’s and funded by Cancer Focus NI, has helped to shed some light on this question.

 

The research demonstrates that when estrogen, which is highest in breast and ovarian tissues, is metabolically broken down, its metabolic by-products induce high levels of a severe DNA damage within these cells.

 

The research also shows that BRCA1 is not only needed to repair this damage (helping to prevent cancer in these cells), but BRCA1 itself slows down the metabolism of estrogen in breast cells, thereby reducing the damage to DNA caused by estrogen.

 

This research suggests that it may be possible to use currently available drugs that reduce estrogen levels to prevent breast and ovarian cancer in women with a BRCA1 mutation. Currently, the only preventative option for women with these mutations is risk reducing surgery to remove their breasts and/or ovaries.

Download the full Oncogene Paper here. 

  1. Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

This research paper describes a brand new function for the BRCA1 gene. The research illustrates how the BRCA1 protein can work with at least 12 other genes to help fix damaged DNA and prevent cancer.

 

These 12 new genes that help BRCA1 do this are themselves mutated or ‘turned off’ in a variety of different cancer types, and the study shows that because of the way they work with BRCA1, we might be able to treat cancers which have turned these genes off with more targeted, less toxic treatments in the future.

Read the full research paper here.

  

Dr Savage biography

Dr Savage received a first class honours Bachelor of Biomedical Science degree from Griffith University, Brisbane. He also gained a Bachelor of Medicine and Bachelor of Surgery combined with a PhD specialising in Oncology at the University of Queensland, a research-intensive institution in the top 1% of universities worldwide.

 

Moving to QUB in 2007, Dr Savage completed a post-doctoral research programme with Professor Paul Harkin, working on hereditary breast cancer.

 

If you want to find out more or make a funding request for your research project, contact  Julie on juliemcconville@cancerfocusni.org  or 028 9066 3281.