Increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of bladder cancer

Abstract

Background:Bladder cancer (BC) is among the most common malignancies worldwide. The identification of new biomarkers for early BC detection, recurrence/progression is urgently needed. The cytokinesis-block micronucleus assay (CBMN) evaluates chromosome damage in cultured human lymphocytes and micronuclei (MN) provide a convenient and reliable index of both chromosome breakage and loss.Methods:Chromosomal damage (expressed as frequencies of MN, nucleoplasmic bridges and nuclear buds (NBUD)) was evaluated by CBMN assay in cryopreserved lymphocytes from 158 age/smoking-matched pairs of cases and controls in relation to BC risk, recurrence or progression. Moreover, non-muscle invasive BC (NMIBC) patients were characterised for 783 DNA repair gene polymorphisms for their possible association with the investigated cytogenetic end points.Results:MN and NBUD frequencies were significantly higher in cases than in controls (P=0.001 and P=0.006, respectively), with the associations being stronger in NMIBC. In a logistic regression model, for each increase of one unit in the MN frequency, a 1.12 increased risk of developing NMIBC was observed. In NMIBC cases, 10 polymorphisms were associated with different MN frequencies after genotype stratification.Conclusions:A model including traditional BC risk factors, MN frequency and the selected polymorphisms differentially distributed in cases and controls improved BC patient identification. Understanding the meaning of systemic chromosomal damage in BC patients with respect to the general population may help to adopt specific prevention strategies and therapeutic intervention.

Micronuclei frequency in urothelial cells of bladder cancer patients, as a biomarker of prognosis

“…Another explanation may involve the genomic instability present in individuals developing BC. The existence of genomic instability is supported by the fact that BC patients present elevated frequency of MN not only in urothelial cells, but also in other cell types such as lymphocytes (Pardini et al, ), and oral mucosa cells (Feki‐Tounsi et al, ). The existence of genomic instability in these patients has been already proposed suggesting the existence of genetic unstable cells in the normal appearing urotelium of resected patients (Gontijo et al, ).…”

“…The elevated incidence of this pathology has move many researchers to look for biomarkers of early detection of its recurrence/progression. In this way, a recent association study has shown that MN in PBL is a suitable biomarker of BC risk, since MN frequencies were significantly higher in BC patients than in controls (Pardini et al, ). Nevertheless, MN frequency in PBL is considered a general biomarker more than a specific one of a particular type of cancer.…”

“…E-mail: ricard. marcos@uab.es; susana.pastor@uab.es of BC risk, since MN frequencies were significantly higher in BC patients than in controls (Pardini et al, 2017). Nevertheless, MN frequency in PBL is considered a general biomarker more than a specific one of a particular type of cancer.…”

Effects of Micronucleus Frequencies and Mitochondrial DNA Copy Numbers among Benzene‐Exposed Workers in China

“…Previous reports showed that MN is a highly useful biomarker to assess genotoxicity, e.g. to benzene (Angelini et al 2016) and MN frequencies were associated with risk of cancer (Lovreglio et al 2014;Pardini et al 2017;Zhang et al 2019). Our study shows significant and dosedependent increase of MN frequencies among workers with very low exposure doses to benzene.…”

An Automated, Single Cell Quantitative Imaging Microscopy Approach to Assess Micronucleus Formation, Genotoxicity and Chromosome Instability

“…In this regard, numerous cytological studies have identified micronuclei within various cancer contexts including head and neck, ovarian, and breast cancers [9][10][11]. Interestingly, the presence of micronuclei in precursor lesions is associated with an increased risk of developing certain cancers [12][13][14][15], suggesting that the presence and frequency of micronuclei may hold clinical value as diagnostic and prognostic biomarkers. Thus, the ability to accurately identify and enumerate micronuclei is relevant in both laboratory and clinical settings.…”