Abstract
The micronucleus test is a well-established DNA damage assay in human monitoring. The test was proposed as a promising marker of cancer risk/susceptibility mainly on the basis of studies on breast cancer. Our recent meta-analysis showed that the association between micronuclei frequency, either at baseline or after irradiation, and breast cancer risk or susceptibility, has been evaluated in few studies of small size, with inconsistent results. The aim of the present study is to investigate the role of micronucleus assay in evaluating individual breast cancer susceptibility. Two-hundred and twenty untreated breast cancer patients and 295 female controls were enrolled in the study. All women were characterized for cancer family history and 155 subjects were evaluated for the presence of BRCA mutations. Micronuclei frequency was evaluated at baseline and after irradiation with 1-Gy gamma rays from a 137Cs source. The results show a non significant increase of frequency of micronucleated binucleated lymphocytes in cancer patients compared with the controls at baseline (Mean (S.E.): 16.8 (0.7) vs 15.7 (0.5), but not after irradiation (Mean (S.E.): 145.8 (3.0) vs 154.0 (2.6)). Neither a family history of breast cancer nor the presence of a pathogenic mutation in BRCA1/2 genes were associated with an increased micronuclei frequency. Our results do not support a significant role of micronucleus frequency as a biomarker of breast cancer risk/susceptibility.
Highlights
The cytokinesis-block micronucleus assay (CBMN assay), due to its ability to detect both structural and numerical chromosomal aberrations, is one of the most successful assays in genetic toxicology and mutation research.In vitro, it is recommended in the basic battery of tests to screen new chemical and physical agents for genotoxicity [1]
The obvious bias deriving from the setting where cases and controls were selected affects the relative frequency of women with a positive family history of breast cancer (BC) and/or a BRCA mutation, but does not affect the endpoint of our study, that is, the MN frequency in these different groups of women
The aim of the present study was to evaluate the potential role of micronucleus test in identifying a susceptibility to BC related to familiar or genetic factors
Summary
The cytokinesis-block micronucleus assay (CBMN assay), due to its ability to detect both structural and numerical chromosomal aberrations, is one of the most successful assays in genetic toxicology and mutation research In vitro, it is recommended in the basic battery of tests to screen new chemical and physical agents for genotoxicity [1]. Assessment of the risk of developing cancer and other chronic diseases, as a marker of ‘‘early damage’’. In this perspective, CBMN could represent a formidable tool for epidemiological studies. Its use in evaluating the individual susceptibility to potentially genotoxic exposures could be even more important for clinical and epidemiological studies and for preventive interventions, because CBMN could be used to identify individuals at high risk of developing a given disease, and could even qualify as an intermediate biomarker (surrogate endpoint) to assess the effects of preventive measures. The overall evidence from studies aimed at assessing these two potential applications is inconclusive
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