title: 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.
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.|Department of Medical Sciences, University of Turin, Via Santena 19, Turin 10126, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.|Department of Medical Sciences, University of Turin, Via Santena 19, Turin 10126, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Viberti
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.|Department of Medical Sciences, University of Turin, Via Santena 19, Turin 10126, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Allione
authors.affiliation: Department of Urology, Città della Salute e della Scienza, Corso Bramante 88, Turin 10126, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Oderda
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Critelli
authors.affiliation: Department of Urology, Città della Salute e della Scienza, Corso Bramante 88, Turin 10126, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Preto
authors.affiliation: Department of Environment and Primary prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zijno
authors.affiliation: Department of Urology, Clinica Cellini, Via Cellini 5, Turin 10126, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Cucchiarale
authors.affiliation: Department of Urology, Città della Salute e della Scienza, Corso Bramante 88, Turin 10126, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.|Department of Epidemiology and Public Health, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: Unit of Cancer Epidemiology, Center for Cancer Prevention (CPO-Piemonte), Via Santena 7, Turin 10126, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: Human Genetics Foundation-Torino (HuGeF), via Nizza 52, Turin 10126, Italy.|Department of Medical Sciences, University of Turin, Via Santena 19, Turin 10126, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matullo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor