Increased radiosensitivity as an indicator of genes conferring breast cancer susceptibility.
OBJECTIVE
This paper briefly summarizes the research on increased radiosensitivity in breast cancer patients measured by the micronucleus test (MNT) and its association to genetic variants in DNA repair genes. More preliminary data are presented on the distribution of chromosomes and chromosome fragments in micronuclei (MN) in order to gain more information on clastogenic and aneugenic effects and better understand the phenotype of increased radiosensitivity.


METHODS
Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. In four patients with high MN frequency (three cancer patients, one control) and four probands with low MN frequency, the presence of chromosome fragments or whole chromosomes in MN was determined by fluorescence in situ hybridization analysis for chromosomes 1, 7, and 17.


RESULTS
An increased MN frequency in breast cancer patients compared to controls has consistently been reported with high significance. Higher MN frequencies were observed in 20-50% of breast cancer patients. Chromosomal fragments of chromosome 17, but not of chromosomes 1 and 7 were more frequent in the probands with high MN frequency than in those with low frequency (p = 0.045).


CONCLUSIONS
The MNT detects a cellular phenotype common to a portion of sporadic breast cancer patients. This phenotype is very likely to be genetically determined. For the genetic dissection of breast cancer susceptibility this phenotype may turn out to be more efficient than breast cancer itself. Additional parameters which can be measured simultaneously with the MN frequency may be able to further enhance its usefulness.
Department of Gynecology and Obstetrics, University of Ulm Medical School, Ulm, Germany.
Dominic
D
Varga
Walther
W
Vogel
Ariane
A
Bender
Harald
H
Surowy
Christiane
C
Maier
Rolf
R
Kreienberg
Helmut
H
Deissler
Georg
G
Sauer
D000782:Aneuploidy; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics / Q000528:radiation effects; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics / Q000528:radiation effects; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000528:radiation effects; D004252:DNA Mutational Analysis; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015162:Micronucleus Tests; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics*