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

Kikuchi A, Yamaya M, Suzuki S, Yasuda H, Kubo H, Nakayama K, Handa M, Sasaki T, Shibahara S, Sekizawa K, Sasaki H

Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

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.

Published 4 April 2005 in Hum Genet, 116(5): 354-60.
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