Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism
Association of susceptibility to the development of lung adenocarcinoma with the heme oxygenase-1 gene promoter polymorphism
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DOI：
10.1007/s00439-004-1162-2
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发表时间：
2005-04-01
期刊：
影响因子：
5.3
通讯作者：
Sasaki, H
中科院分区：
文献类型：
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作者：
Kikuchi, A;Yamaya, M;Sasaki, H
血红素加氧酶-1（HO-1）在香烟烟雾中对氧化剂和芳香烃的细胞保护作用。人HO-1基因5 '侧翼区的一个（GT）（n）二核苷酸重复序列（别名HMOX 1）可减少HO-1的诱导作用，并显示出长度多态性，其分为三类：S类（< 27 GT）、M类（27-32 GT）和L类（>= 33 GT）等位基因。为了研究HO-1基因多态性与肺腺癌发生的相关性，我们筛选了151例日本肺腺癌患者和153例对照组。患者和对照组受试者的年龄，性别，吸烟史和慢性肺气肿的比例频率匹配。肺腺癌患者的L类等位基因频率比例以及L等位基因携带者（LL、LM和LS）的基因型频率比例均显著高于对照组。L类等位基因携带者与非L类等位基因携带者（M+S）肺腺癌的校正比值比（OR）为1.6 [95%可信区间（CI）1.0-2.5，P= 0.03]，L类等位基因携带者与非L类等位基因携带者肺腺癌的校正比值比（OR）为1.8（95%CI 1.1-3.0，P=0.02）。男性吸烟者中，L等位基因携带者患肺腺癌的危险性显著高于非L等位基因携带者（OR=3.3，95% CI 1.5-7.4，P=0.004）。而在女性非吸烟者中，L等位基因携带者的比例在两组间无显著性差异（OR=0.93，95% CI 0.4-2.0，P=0.85）。这些发现表明HO-1基因启动子中的a（GT）（n）重复序列的大尺寸可能与日本男性吸烟者肺腺癌的发生有关。
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.