Shiraishi Kouya, Kohno Takashi, Kunitoh Hideo, Watanabe Shun-ichi, Goto Koichi, Nishiwaki Yutaka, Shimada Yoko, Hirose Hiroshi, Saito Ikuo, Kuchiba Aya, Yamamoto Seiichro, Yokota Jun
Biology Division, National Cancer Center Research Institute, National Cancer Center Hospital, Tokyo, Japan.
Carcinogenesis. 2009 Jan;30(1):65-70. doi: 10.1093/carcin/bgn257. Epub 2008 Nov 12.
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.
近期针对欧美人群的全基因组关联（GWA）研究显示，在包含两个烟碱型乙酰胆碱受体（CHRNA）基因的位点上，单核苷酸多态性（SNP）与肺癌风险存在关联，此前已有研究表明该基因与烟草成瘾有关。在这些研究中，一致观察到SNP与吸烟者肺癌风险存在关联，但在非吸烟者中以及与吸烟行为的关联并不一致。为了进一步了解CHRNA SNP在肺癌风险中的意义，我们通过一项病例对照研究，在1250例病例（562例腺癌、391例鳞状细胞癌和297例小细胞癌）和936例对照的日本人群中，检测了该位点的7个SNP与肺癌风险以及吸烟状况的关联。在GWA研究中被定义为易感单倍型的由rs8034190、rs16969968和rs1051730这三个SNP的次要等位基因组成的单倍型，在日本人群中的频率（0.013）远低于欧美人群（0.3 - 0.4）。然而，在日本人中，这种单倍型也与肺癌风险显著相关（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均观察到这种关联。具有这种单倍型的个体的吸烟剂量高于没有这种单倍型的个体；然而，差异无统计学意义。这些结果有力地表明，CHRNA SNP以与吸烟无关的方式使一小部分日本人易患肺癌。
