title: The cytokinesis-blocked micronucleus assay as a strong predictor of lung cancer: extension of a lung cancer risk prediction model.
abstract: BACKGROUND
  There is an urgent need to improve lung cancer outcome by identifying and validating markers of risk. We previously reported that the cytokinesis-blocked micronucleus assay (CBMN) is a strong predictor of lung cancer risk. Here, we validate our findings in an independent external lung cancer population and test discriminatory power improvement of the Spitz risk prediction model upon extension with this biomarker.
  
  
  METHODS
  A total of 1,506 participants were stratified into a test set of 995 (527 cases/468 controls) from MD Anderson Cancer Center (Houston, TX) and a validation set of 511 (239 cases/272 controls) from Massachusetts General Hospital (Boston, MA). An epidemiologic questionnaire was administered and genetic instability was assessed using the CBMN assay.
  
  
  RESULTS
  Excellent concordance was observed between the two populations in levels and distribution of CBMN endpoints [binucleated-micronuclei (BN-MN), binucleated-nucleoplasmic bridges (BN-NPB)] with significantly higher mean BN-MN and BN-NPB values among cases (P < 0.0001). Extension of the Spitz model led to an overall improvement in the AUC (95% confidence intervals) from 0.61 (55.5-65.7) with epidemiologic variables to 0.92 (89.4-94.2) with addition of the BN-MN endpoint. The most dramatic improvement was observed with the never-smokers extended model followed by the former and current smokers.
  
  
  CONCLUSIONS
  The CBMN assay is a sensitive and specific predictor of lung cancer risk, and extension of the Spitz risk prediction model led to an AUC that may prove useful in population screening programs to identify the "true" high-risk individuals.
  
  
  CONCLUSIONS
  Identifying high-risk subgroups that would benefit from screening surveillance has immense public health significance.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. relzein@mdanderson.org.
authors.forename: Randa A
authors.initials: RA
authors.lastname: El-Zein
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mirtha S
authors.initials: MS
authors.lastname: Lopez
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: D'Amelio
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. CORRONA, Inc., Southborough, Massachusetts.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.affiliation: Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas. Houston Methodist, Houston, Texas.
authors.forename: Reginald F
authors.initials: RF
authors.lastname: Munden
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: David
authors.initials: D
authors.lastname: Christiani
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Paula
authors.initials: P
authors.lastname: Tejera-Alveraz
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Rihong
authors.initials: R
authors.lastname: Zhai
authors.affiliation: Dan L. Duncan Cancer Center, Houston, Texas.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas. CORRONA, Inc., Southborough, Massachusetts.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
mesh_terms: D048749:Cytokinesis / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011795:Surveys and Questionnaires