On the difference of micronucleus frequencies in peripheral blood lymphocytes between breast cancer patients and controls.
Sporadic breast cancer patients as well as mutation carriers of the BRCA genes have a reduced DNA repair capacity compared to controls when assessed by the G0 micronucleus test (G(0)MNT) or by induced chromosomal aberrations. Since the individual MN frequencies vary widely and overlap between cases and controls it remained unclear which percentage of the cases should be considered to exhibit an increased radiosensitivity. We performed a similar case-control study and found a highly significant difference (P < 0.0001) between all breast cancer cases (N = 91) and female controls (N = 96) using descriptive statistics and ANOVA with adjustment for age. This difference also holds for baseline MN frequencies (P = 0.0006) and for subgroups of the patients similar to those without treatment (P < 0.0001). These results were confirmed in a second sample acquired at a different hospital. Since we are dealing in this analysis with two predefined groups (patients and controls), we calculated odds ratios (ORs) in order to assess the discriminative power of the G0 MNT. These amounted to OR = 4.9 (P < 0.0001) for MN frequencies obtained by visual counting and ranged from OR = 11 (P < 0.0011) to OR = 22 (P < 0.0001) using automated counting. In order to overcome the problem of choosing a cut-off point inherent in ORs, receiver operating characteristic curves were calculated, which visualize specificity and sensitivity over the entire range of values and which characterize the discriminative power of a test by the area under the curve (AUC) (visual counting, baseline: AUC = 0.67; induced AUC = 0.75; automated counting: AUC > 0.88; evaluation sample: AUC > 0.73). We conclude that the G0 MNT may be a useful tool to substitute the phenotype breast cancer in association and linkage studies and that it may be possible to develop a test useful in the diagnosis or risk assessment for breast cancer.
Varga
Dominic
D
Department of Human Genetics, University of Ulm, Ulm, Germany.
Hoegel
Josef
J
Maier
Christiane
C
Jainta
Silke
S
Hoehne
Maren
M
Patino-Garcia
Brenda
B
Michel
Isabell
I
Schwarz-Boeger
Ulrike
U
Kiechle
Marion
M
Kreienberg
Rolf
R
Vogel
Walther
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair; D003627:Data Interpretation, Statistical; D005260:Female; D006580:Genetic Carrier Screening / Q000379:methods; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008214:Lymphocytes / Q000648:ultrastructure*; D048629:Micronuclei, Chromosome-Defective / Q000706:statistics & numerical data; D015162:Micronucleus Tests / Q000379:methods*; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D012680:Sensitivity and Specificity
D019313:BRCA1 Protein