Breast cancer genetic variants identified
Tuesday March 1st, 2016
Five genetic variants that affect the risk of breast cancer and are linked to oestrogen receptors have been identified in an international study.
The
findings suggest that a “Goldilocks” level of receptors is
needed in breast cells, the researchers say - not too few and not too
many.
The research, which involved almost 120,000 women, found the cancer-risk variants based within or around the DNA surrounding the gene for the oestrogen receptor, called the ESR1 gene.
Although this gene is known to be related to the risk and progress of breast cancer, it was not understood how it works and why it affects breast cancers.
The researchers studied ESR1 in women with different types of breast cancer and compared them with healthy controls.
The international collaboration, led by researchers at the University of Cambridge in England and the QIMR Berghofer Medical Research Institute, Brisbane, Australia, found that four of the variants were more strongly linked to tumours where the ESR1 gene is switched off.
The study, published in Nature Genetics is believed to be the first time a specific genetic risk factor for human epidermal growth factor 2 (HER2) has been linked to a rare type of breast tumour.
The QIMR Berghofer team, led by Dr Stacey Edwards said there are two major types of gene regulators: enhancers, which increase activity of the genes express, and silencers, which have the opposite effect.
However, when the Cambridge and Brisbane teams worked together, they discovered that four of the breast cancer risk variants coincided with the enhancers, affecting nearby genes and the ESR1 gene.
They report that the variants which increased the risk of breast cancer directly reduced the effectiveness of each enhancer, which in turn cut the amount of oestrogen receptor produced by breast cells.
The fifth genetic variant was found to associated more with tumours where the oestrogen receptor is switched on, which increases the amount of oestrogen receptor protein that are produced by breast cells.
Dr Alison Dunning from the Department of Oncology at the University of Cambridge, one of the lead authors, said: “It's interesting that all five of the genetic variants that we have found affect levels of oestrogen receptors in breast cells.
“This suggests that there may be a 'Goldilocks' level of these receptors in breast cells: too few or too many and the breast cells are more likely to become cancerous.”
Dr Edwards said the findings could pave the way for the development of new, more specific breast cancer preventions.
“As our research looks at how tumours with and without the oestrogen receptor are regulated, it's possible it could help make sense of the enduring mystery of how tamoxifen works and why tumours develop in these two divergent ways,” she added.
Dr Alan Worsley, Cancer Research UK's senior science information officer, said the study adds more detail to the genetic map of breast cancer risk.
“Understanding more about each individual's risk of cancer could help us find ways to potentially prevent the disease or pick it up in its earliest stages,” he added.
Dunning, AM et al. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nature Genetics 29 February 2016; doi:10.1038/ng.3521
Tags: Australia | Cancer | Genetics | UK News | Women's Health & Gynaecology
Printer friendly page