Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese
Contribution of nicotine acetylcholine receptor polymorphisms to lung cancer risk in a smoking-independent manner in the Japanese
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DOI：
10.1093/carcin/bgn257
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发表时间：
2009-01-01
期刊：
影响因子：
4.7
通讯作者：
Yokota, Jun
中科院分区：
文献类型：
--
作者：
Shiraishi, Kouya;Kohno, Takashi;Yokota, Jun
最近针对欧洲和美洲人群的全基因组关联（GWA）研究揭示了含有两个尼古丁乙酰胆碱受体（CHRNA）基因的基因座中的单核苷酸多态性（SNP）与肺癌风险的关联，这两个基因与烟草成瘾有关。在这些研究中观察到，吸烟者与肺癌风险的关联是一致的，但非吸烟者以及吸烟行为的关联却不一致。为了获得有关 CHRNA SNP 在肺癌风险中的重要性的更多信息，通过一项病例对照研究，在日本人群中检查了该位点的 7 个 SNP 与肺癌风险以及吸烟状况的关联，该研究涉及 1250 例病例（562 例腺癌、391 例鳞状细胞癌和 297 例小细胞癌）和 936 例对照。由 rs8034190、rs16969968 和 rs1051730 三个 SNP 的次要等位基因组成的单倍型（在 GWA 研究中被定义为易感单倍型）在日本人群中的频率 (0.013) 远低于欧洲和美洲人群 (0.3-0.4)。然而，这种单倍型在日本人中也与肺癌风险显着相关（优势比 = 2.3，95% 置信区间 = 1.5-3.7，P = 0.00028）。在吸烟者和非吸烟者以及所有组织学类型的肺癌中都观察到了这种关联。具有这种单倍型的个体比没有这种单倍型的个体表现出更高的吸烟剂量。然而，差异没有统计学意义。这些结果强烈表明，CHRNA SNP 以与吸烟无关的方式赋予一小部分日本人肺癌易感性。
Recent genome wide association (GWA) studies on European and American populations revealed association with lung cancer risk of single-nucleotide polymorphisms (SNPs) in the locus containing two nicotine acetylcholine receptor (CHRNA) genes, whose involvement in tobacco addiction had been indicated. Association with lung cancer risk in smokers was consistently, but that in non-smokers as well as that with smoking behavior was inconsistently, observed in these studies. To obtain further information on the significance of CHRNA SNPs in lung cancer risk, association of seven SNPs in this locus with lung cancer risk as well as smoking status was examined in a Japanese population by a case-control study of 1250 cases (562 adenocarcinoma, 391 squamous cell carcinoma and 297 small cell carcinoma) and 936 controls. The frequency of the haplotype consisting of minor alleles for three SNPs, rs8034190, rs16969968 and rs1051730, which had been defined as a susceptible haplotype in the GWA studies, was much lower in the Japanese population (0.013) than in European and American populations (0.3-0.4). However, this haplotype was significantly associated with lung cancer risk also in Japanese (odds ratio = 2.3, 95% confidence interval = 1.5-3.7, P = 0.00028, respectively). The association was observed both in smokers and non-smokers and in all histological types of lung cancers. Individuals with this haplotype showed higher smoking doses than those without; however, the difference was not statistically significant. These results strongly indicate that CHRNA SNPs confer lung cancer susceptibility in a small subset of Japanese in a smoking-independent manner.