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

Barbara Pardini, Clara Viberti, Alessio Naccarati, Alessandra Allione, Marco Oderda, Rossana Critelli, Mirko Preto, Andrea Zijno, Giuseppina Cucchiarale, Paolo Gontero, Paolo Vineis, Carlotta Sacerdote, Giuseppe Matullo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)202-210
Number of pages9
JournalBritish Journal of Cancer
Volume116
Issue number2
DOIs
Publication statusPublished - Jan 17 2017
Externally publishedYes

Keywords

  • bladder cancer
  • micronucleus assay
  • peripheral blood mononuclear cells
  • risk prediction

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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