A polymorphism of C-to-T substitution at-31IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population
A polymorphism of C-to-T substitution at-31IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population
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DOI：
10.1007/s10038-006-0040-2
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Tajima, Kazuo
中科院分区：
文献类型：
--
作者：
Ikehara, Sanae Kabata;Ikehara, Yuzuru;Tajima, Kazuo
促炎性细胞因子基因多态性与胃癌的易感性有关，其中IL-1B-31T/C和-511C/T的变化可能会改变IL-1B的转录，因此已被广泛研究。白介素1β(IL1β)刺激下的信号转导靶点是核因子kappa B(NF Kappa B)的激活，它支持肿瘤的发展，其中信号转导是由FS-7细胞相关细胞表面抗原(Fas)信号介导的。根据最近的文献，我们试图确定IL-1B-31/-511和Fas-670基因的多态是否会影响日本胃癌患者的预后。对271例胃腺癌患者和271例年龄性别频率匹配的对照组进行病例对照研究。在病例组和对照组中，IL1B的T等位基因-511和C等位基因-31以及C等位基因-511和T等位基因-31之间存在强连锁不平衡(R-2=0.94)。IL1B-31、-511和Fas-670基因多态与胃腺癌发病风险均无显著差异。Fas-670等位基因频率差异无统计学意义，但IL-1B-31TT(或IL-1B-511CC)携带者比例随临床分期增加而增加(趋势P=0.019)。特别是，与I期患者相比，IV期患者具有IL1B-31TT(或IL1B-511CC)基因的概率高两倍。这些观察结果表明，IL1B-31TT和IL1B-511CC与疾病进展有关。
Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1 beta) stimulation, the nuclear factor of kappa B (NF kappa B) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NF kappa B functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B-31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R-2 = 0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.