title: Increased methylation of lung cancer-associated genes in sputum DNA of former smokers with chronic mucous hypersecretion.
abstract: BACKGROUND
  Chronic mucous hypersecretion (CMH) contributes to COPD exacerbations and increased risk for lung cancer. Because methylation of gene promoters in sputum has been shown to be associated with lung cancer risk, we tested whether such methylation was more common in persons with CMH.
  
  
  METHODS
  Eleven genes commonly silenced by promoter methylation in lung cancer and associated with cancer risk were selected. Methylation specific PCR (MSP) was used to profile the sputum of 900 individuals in the Lovelace Smokers Cohort (LSC). Replication was performed in 490 individuals from the Pittsburgh Lung Screening Study (PLuSS).
  
  
  RESULTS
  CMH was significantly associated with an overall increased number of methylated genes, with SULF2 methylation demonstrating the most consistent association. The association between SULF2 methylation and CMH was significantly increased in males but not in females both in the LSC and PLuSS (OR = 2.72, 95% CI = 1.51-4.91, p = 0.001 and OR = 2.97, 95% CI = 1.48-5.95, p = 0.002, respectively). Further, the association between methylation and CMH was more pronounced among 139 male former smokers with persistent CMH compared to current smokers (SULF2; OR = 3.65, 95% CI = 1.59-8.37, p = 0.002).
  
  
  CONCLUSIONS
  These findings demonstrate that especially male former smokers with persistent CMH have markedly increased promoter methylation of lung cancer risk genes and potentially could be at increased risk for lung cancer.
authors.forename: Shannon
authors.initials: S
authors.lastname: Bruse
authors.forename: Hans
authors.initials: H
authors.lastname: Petersen
authors.forename: Joel
authors.initials: J
authors.lastname: Weissfeld
authors.forename: Maria
authors.initials: M
authors.lastname: Picchi
authors.forename: Randall
authors.initials: R
authors.lastname: Willink
authors.forename: Kieu
authors.initials: K
authors.lastname: Do
authors.forename: Jill
authors.initials: J
authors.lastname: Siegfried
authors.forename: Steven A
authors.initials: SA
authors.lastname: Belinsky
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, NM, Mexico. ytesfaig@lrri.org.
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D013183:Sputum / Q000378:metabolism*