Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86140
Title:
Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy.
Authors:
Scott, David
Abstract:
AIM: This paper briefly summarizes the research on this topic, undertaken in the Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, England, over the previous 6 years. PATIENTS AND METHOD: Patients with the recessively-inherited disease, ataxia-telangiectasia (A-T), who are cancer-prone and suffer severe reactions after radiotherapy, also have highly radiosensitive cells, particularly when chromosome damage is used as the measure of radiosensitivity. Enhanced chromosomal radiosensitivity is also a feature of many other cancer-prone disorders. We have investigated the possible role of such radiosensitivity as a marker of cancer predisposition and response to radiotherapy in the general population. RESULTS: We found that 42% (57/135) of breast cancer patients exhibit chromosomal radiosensitivity when lymphocytes are irradiated in the G2 phase of the cell cycle, compared with 6% (6/105) of healthy controls (Figure 1). These figures are much higher than the estimated frequencies of carriers of the ataxia-telangiectasia gene (heterozygotes) amongst breast cancer patients (< 5%) and controls (0.5%). We have also obtained evidence of heritability of G2 sensitivity by studying relatives of breast cancer cases (Figures 2 and 3). The pattern of inheritance is relatively simple and attributable to 1 or 2 genes segregating in each family (Figure 4). In a prospective study of 123 breast cancer patients, 9 (7%) had severe acute reactions to radiotherapy and their mean G2 sensitivity was significantly greater (p = 0.001) than that of the remaining patients (Figure 5). In 16 patients with adverse acute reactions we found no mutations of the ataxia-telangiectasia gene (ATM). Using another chromosomal assay (micronucleus induction in G0 lymphocytes) we found that the mean radiosensitivity of patients with severe late reactions was higher than that of normal reactors. For example, 8 patients with severe fibrosis were more sensitive (p = 0.055) than 39 patients with a normal response (Figure 6). However, the discriminatory power of these chromosomal assays is too low for them to be used alone in a clinical setting. CONCLUSION: Our results provide good evidence that genes other than ATM, that confer chromosomal radiosensitivity, are involved in low penetrance predisposition to breast cancer in a high proportion of cases and contribute to adverse reactions after radiotherapy.
Affiliation:
Department of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK. dscott@picr.man.ac.uk
Citation:
Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy. 2000, 176 (5):229-34 Strahlenther Onkol
Journal:
Strahlentherapie und Onkologie
Issue Date:
May-2000
URI:
http://hdl.handle.net/10541/86140
PubMed ID:
10847120
Type:
Article
Language:
en
ISSN:
0179-7158
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorScott, Daviden
dc.date.accessioned2009-11-13T13:17:34Z-
dc.date.available2009-11-13T13:17:34Z-
dc.date.issued2000-05-
dc.identifier.citationChromosomal radiosensitivity, cancer predisposition and response to radiotherapy. 2000, 176 (5):229-34 Strahlenther Onkolen
dc.identifier.issn0179-7158-
dc.identifier.pmid10847120-
dc.identifier.urihttp://hdl.handle.net/10541/86140-
dc.description.abstractAIM: This paper briefly summarizes the research on this topic, undertaken in the Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, England, over the previous 6 years. PATIENTS AND METHOD: Patients with the recessively-inherited disease, ataxia-telangiectasia (A-T), who are cancer-prone and suffer severe reactions after radiotherapy, also have highly radiosensitive cells, particularly when chromosome damage is used as the measure of radiosensitivity. Enhanced chromosomal radiosensitivity is also a feature of many other cancer-prone disorders. We have investigated the possible role of such radiosensitivity as a marker of cancer predisposition and response to radiotherapy in the general population. RESULTS: We found that 42% (57/135) of breast cancer patients exhibit chromosomal radiosensitivity when lymphocytes are irradiated in the G2 phase of the cell cycle, compared with 6% (6/105) of healthy controls (Figure 1). These figures are much higher than the estimated frequencies of carriers of the ataxia-telangiectasia gene (heterozygotes) amongst breast cancer patients (< 5%) and controls (0.5%). We have also obtained evidence of heritability of G2 sensitivity by studying relatives of breast cancer cases (Figures 2 and 3). The pattern of inheritance is relatively simple and attributable to 1 or 2 genes segregating in each family (Figure 4). In a prospective study of 123 breast cancer patients, 9 (7%) had severe acute reactions to radiotherapy and their mean G2 sensitivity was significantly greater (p = 0.001) than that of the remaining patients (Figure 5). In 16 patients with adverse acute reactions we found no mutations of the ataxia-telangiectasia gene (ATM). Using another chromosomal assay (micronucleus induction in G0 lymphocytes) we found that the mean radiosensitivity of patients with severe late reactions was higher than that of normal reactors. For example, 8 patients with severe fibrosis were more sensitive (p = 0.055) than 39 patients with a normal response (Figure 6). However, the discriminatory power of these chromosomal assays is too low for them to be used alone in a clinical setting. CONCLUSION: Our results provide good evidence that genes other than ATM, that confer chromosomal radiosensitivity, are involved in low penetrance predisposition to breast cancer in a high proportion of cases and contribute to adverse reactions after radiotherapy.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subject.meshAtaxia Telangiectasia-
dc.subject.meshBreast Neoplasms-
dc.subject.meshChromosome Aberrations-
dc.subject.meshChromosomes, Human-
dc.subject.meshFemale-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHumans-
dc.subject.meshLymphocytes-
dc.subject.meshMale-
dc.subject.meshMicronucleus Tests-
dc.subject.meshMutagenicity Tests-
dc.subject.meshPedigree-
dc.subject.meshRadiation Tolerance-
dc.subject.meshReference Values-
dc.subject.meshReproducibility of Results-
dc.titleChromosomal radiosensitivity, cancer predisposition and response to radiotherapy.en
dc.typeArticleen
dc.contributor.departmentDepartment of Cancer Genetics, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Withington, Manchester, UK. dscott@picr.man.ac.uken
dc.identifier.journalStrahlentherapie und Onkologieen
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