POLQ gene overexpression linked to breast cancer relapse
MedWire News: UK researchers have discovered that overexpression of the DNA polymerase theta gene (POLQ) is associated with a substantially increased risk for breast cancer relapse.
The team from the University of Oxford suggests drugs that block POLQ may be able to reverse the very poor survival associated with over-production of this gene.
"Depletion of POLQ has recently been shown to render tumor cells more sensitive to radiotherapy whilst having little or no effect on normal tissues," explain W Gillies McKenna and colleagues in the open access journal Oncotarget.
This finding led the researchers to investigate whether tumors that overexpress POLQ are associated with adverse outcomes in breast cancer patients. They assessed POLQ expression levels in tumor samples from 279 patients treated for early-stage disease between 1989 and 1998, then correlated their findings with the clinical outcomes of each of the patients.
McKenna and team found that a significant number of tumors overexpressed POLQ and that overexpression significantly correlated with estrogen receptor (ER)-negative disease and high tumor grade, both of which are associated with poor clinical outcome.
Multivariate analysis revealed that POLQ overexpression was independently associated with an eight-fold increased risk for relapse, after adjustment for ER status, lymph node status, patient age, tumor grade, and tumor size.
Analysis of genetic data from several other studies of more than 800 breast cancer patients in the UK, The Netherlands, and Sweden confirmed that POLQ overexpression is associated with adverse clinical outcomes including cancer development and progression.
The mechanism that causes this adverse outcome is unclear but may, in part, arise from resistance to adjuvant treatment, say McKenna et al. It is also possible that POLQ overexpression promotes a more aggressive phenotype that increases the likelihood of disease recurrence.
McKenna said: "This is important research which provides evidence that POLQ may be a very appealing target for drug development.
"As POLQ is not switched on by most healthy tissues it is possible that if drugs could be developed to block this gene, they would make tumors more responsive to treatments such as radiotherapy and chemotherapy but not increase the side effects caused to healthy cells."
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By Laura Dean