Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism

Hum Genet. 2005 Apr;116(5):354-60. doi: 10.1007/s00439-004-1162-2. Epub 2005 Feb 2.


Heme oxygenase-1 (HO-1) acts in cytoprotection against oxidants and aromatic hydrocarbons in cigarette smoke. A (GT)(n) dinucleotide repeat in the 5'-flanking region of the human HO-1 gene (alias HMOX1) reduces HO-1 inducibility and shows length polymorphism, which is grouped into three classes: class S (<27 GT), class M (27-32 GT), and class L (>/=33 GT) alleles. To investigate the correlation between the HO-1 gene polymorphism and the development of lung adenocarcinoma, we screened 151 Japanese patients with lung adenocarcinoma and 153 control subjects. Patients and control subjects were frequency-matched by age, gender, smoking history and proportion of chronic pulmonary emphysema. The proportion of class L allele frequencies, as well as that of genotypic frequencies in L allele carriers (LL, LM, and LS), were significantly higher in patients with lung adenocarcinoma than those of control subjects. The adjusted odds ratio (OR) for lung adenocarcinoma with class L allele vs non-L allele (M+S) was 1.6 [95% confidence interval (CI) 1.0-2.5, P=0.03] and that with L allele carriers vs. non-L allele carriers was 1.8 (95% CI 1.1-3.0, P=0.02). Furthermore, the risk of lung adenocaricinoma for L allele carriers versus non-L allele carriers was much increased in the group of male smokers (OR=3.3, 95% CI 1.5-7.4, P=0.004). However, in the female non-smokers, the proportion of L allele carriers did not differ between patients and control subjects (OR=0.93, 95% CI 0.4-2.0, P=0.85). These findings suggest that the large size of a (GT)(n) repeat in the HO-1 gene promoter may be associated with the development of lung adenocarcinoma in Japanese male smokers.

MeSH terms

  • 5' Flanking Region
  • Adenocarcinoma / genetics*
  • Aged
  • Case-Control Studies
  • Dinucleotide Repeats
  • Disease Susceptibility
  • Female
  • Gene Frequency
  • Heme Oxygenase (Decyclizing) / genetics*
  • Heme Oxygenase-1
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Membrane Proteins
  • Middle Aged
  • Neoplasms, Squamous Cell / genetics*
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic*
  • Pulmonary Emphysema / complications
  • Smoking


  • Membrane Proteins
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1