Most of the genes found had not been described before and could offer targets for new therapies and strategies to improve diagnosis and prevention of this disease, according to the research led by scientists at the Institute of Cancer Research (ICR) in London. In particular, 32 genes showed a correlation with the duration of survival in women affected by breast cancer.
'These are really important findings. We urgently need to unravel how the genetic changes in the building blocks of our DNA influence a woman's risk of breast cancer, and this study adds another vital piece to this jigsaw,' said Baroness Delyth Morgan, chief executive at the charity Breast Cancer Now, which funded the study.
The team developed a technique called Capture Hi-C to evaluate how DNA sequences from different parts of the genome physically interact. The mechanism that allows distant blocks of DNA to connect is known as DNA looping. They selected 63 regions that were previously linked to breast cancer in genome-wide association studies (GWAS) and found that the breast cancer-related genes were restricted to 33 genomic areas. The remaining 30 regions contained no specific genes.
'Our study took the high-level maps of breast cancer risk regions and used them to pull out specific genes that seem to be associated with the disease,' said Dr Olivia Fletcher, study team leader. 'We studied how DNA forms loops to allow physical interactions between a DNA sequence in one part of the genome and a risk gene in another.'
DNA loops from four different type of breast cancer cells were compared with two normal cell lines and genes involved in looping interactions, specifically in the cancerous cells, were further investigated. The results, published in Nature Communications, led to the discovery of a gene, FADD, already implicated in other cancers and a promising target for novel therapeutic approaches. They also corroborated previous large-scale genetics studies, thanks to identification of 14 genes shown to play a role in breast cancer risk before.
Professor Paul Workman, chief executive of the ICR, noted: 'Large-scale genomic studies have been instrumental in associating areas of our DNA with an increased risk of breast cancer. This study brings these regions of DNA into sharper focus, uncovering a treasure trove of genes that can now be investigated in more detail.'