Increased Micronuclei frequencies in peripheral blood lymphocytes: a marker for cancer risk?

Aims: An increased micronucleus (MN) frequency has been observed in irradiated peripheral lymphocytes of BRCA1 and 2 mutation carriers by micronucleus assay. The same radiosensitivity has been reported for some sporadic breast cancer patients, thus indicating a common cellular phenotype. Methods: Unselected sporadic breast cancer patients (n=140) and controls (n=149) were analysed by the G0 micronucleus test (MNT). In peripheral binucleated blood lymphocytes (BNC) we determined the baseline MN frequency, as well as the MN frequency and the number of BNCs containing two MN after irradiation with 2 Gy. Other cancer samples were investigated using the same approach. Results: Mean induced MN frequencies, BNCs with 2 MN and baseline MN frequencies showed significant differences between patients and controls, with an odds ratio (OR) of 5 to 10 (p<10–4)... Prostate cancer patients (n=20) do not differ from controls (p=0.7), whilst ovarian (n=10) and endometrial cancer (n=8) patients, like those with breast cancer, do differ. Conclusions: Our data suggest that G0 MNT may predict individuals at risk from sporadic breast cancer and other gynaecological malignancies. We hypothesize that the increased sensitivity for irradiation is caused by an intrinsic impairment of the DNA repair pathway and is genetically determined