TY - JOUR
T1 - Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism
AU - Kikuchi, Akiko
AU - Yamaya, Mutsuo
AU - Suzuki, Satoshi
AU - Yasuda, Hiroyasu
AU - Kubo, Hiroshi
AU - Nakayama, Katsutoshi
AU - Handa, Masashi
AU - Sasaki, Takahiko
AU - Shibahara, Shigeki
AU - Sekizawa, Kiyohisa
AU - Sasaki, Hidetada
PY - 2005/4/1
Y1 - 2005/4/1
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-004-1162-2
DO - 10.1007/s00439-004-1162-2
M3 - Article
C2 - 15688187
AN - SCOPUS:20244367472
VL - 116
SP - 354
EP - 360
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 5
ER -