Abstract
Background and PurposeAdjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues. In this respect, individuals with anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular interest as they may be at risk of both breast cancer and clinical radiosensitivity. The association of specific ATM gene mutations with these pathologies has been well documented, however, there is uncertainty regarding pathological thresholds for the ATM protein.ResultsSemi-quantitative immuno-blotting provided a reliable and reproducible method to compare levels of the ATM protein for a rare cohort of 20 cancer patients selected on the basis of their severe adverse normal tissue reactions to radiotherapy. We found that 4/12 (33%) of the breast cancer patients with severe adverse normal tissue reactions following radiotherapy had ATM protein levels < 55% compared to the mean for non-reactor controls.ConclusionsATM mutations are generally considered low risk alleles for breast cancer and clinical radiosensitivity. From results reported here we propose a tentative ATM protein threshold of ~55% for high-risk of clinical radiosensitivity for breast cancer patients.
Highlights
Background and PurposeAdjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues
Breast cancer patients 10, 12 and 13 had relatives diagnosed with breast cancer (Table 1)
3.2 ATM Protein Levels We determined ATM protein levels from lymphoblastoid cell lines (LCLs) established from patients: 52 individuals in total
Summary
Adjuvant radiotherapy for cancer can result in severe adverse side effects for normal tissues In this respect, individuals with anomalies of the ATM (ataxia telangiectasia) protein/gene are of particular interest as they may be at risk of both breast cancer and clinical radiosensitivity. Primary treatment for organ-confined breast cancer usually involves a combination of limited breast-conservation surgery and radiotherapy yielding control rates equivalent to mastectomy. Such radiotherapy is usually tolerated well except for the very small percentage of patients who experience severe adverse normal tissue reactions (RTOG3-4 reactions) [1]. Other genetic predispositions, including autosomal recessive ataxia telangiectasia (A-T), have a clear association with clinical radiosensitivity [6,7]. ATM, the susceptibility gene for A-T, encodes a protein kinase activated in response to ionising
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