title: Epigenetic Repression of CCDC37 and MAP1B Links Chronic Obstructive Pulmonary Disease to Lung Cancer.
abstract: BACKGROUND
  Lung cancer and chronic obstructive pulmonary disease (COPD) share environmental risk factors. COPD also increases the risk of lung cancer; however, the molecular mechanisms are unclear.
  
  
  METHODS
  An epigenome-wide association study of lung tumors and cancer-free lung tissue (CFLT) pairs from non-small-cell lung cancer cases with (n = 18) or without (n = 17) COPD was conducted using the HumanMethylation450 beadchip (HM450K). COPD-associated methylation of top-ranked genes was confirmed in a larger sample set, independently validated, and their potential as sputum-based biomarkers was investigated.
  
  
  RESULTS
  Methylation of CCDC37 and MAP1B was more prevalent in lung tumors from COPD than non-COPD cases [54 of 71 (76%) versus 20 of 46 (43%), p = 0.0013] and [48 of 71 (68%) versus 17 of 46 (37%), p = 0.0035], respectively, after adjustment for age, sex, smoking status, and tumor histology. HM450K probes across CCDC37 and MAP1B promoters showed higher methylation in tumors than CFLT with the highest methylation seen in tumors from COPD cases (p < 0.05). These results were independently validated using The Cancer Genome Atlas data. CCDC37 methylation was more prevalent in sputum from COPD than non-COPD smokers (p < 0.005) from two cohorts. CCDC37 and MAP1B expression was dramatically repressed in tumors and CFLT from COPD than non-COPD cases, p less than 0.02.
  
  
  CONCLUSIONS
  The reduced expression of CCDC37 and MAP1B associated with COPD likely predisposes these genes to methylation that in turn, may contribute to lung cancer.
authors.affiliation: *Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico; †Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania; ‡Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota; and §COPD Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico.
authors.forename: Mathewos
authors.initials: M
authors.lastname: Tessema
authors.forename: Christin M
authors.initials: CM
authors.lastname: Yingling
authors.forename: Maria A
authors.initials: MA
authors.lastname: Picchi
authors.forename: Guodong
authors.initials: G
authors.lastname: Wu
authors.forename: Yushi
authors.initials: Y
authors.lastname: Liu
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.forename: Jill M
authors.initials: JM
authors.lastname: Siegfried
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: Steven A
authors.initials: SA
authors.lastname: Belinsky
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation / Q000235:genetics*; D063185:Epigenetic Repression; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*
chemical_list: C475491:MAP1B protein, human; D008869:Microtubule-Associated Proteins