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NOD2/CARD15 多态性损害固有免疫,增加意大利人群胃癌易感性。

NOD2/CARD15 polymorphisms impair innate immunity and increase susceptibility to gastric cancer in an Italian population.

机构信息

Clinical Pathology, University Campus Bio-Medico, Rome, Italy.

出版信息

Hum Immunol. 2009 Sep;70(9):729-32. doi: 10.1016/j.humimm.2009.04.026. Epub 2009 May 4.

DOI:10.1016/j.humimm.2009.04.026
PMID:19397946
Abstract

In the present case-control study we investigated the potential role of CARD15 R702W, G908R, and 1007fs polymorphisms in Italian gastric cancer patients. The study population consisted of 170 gastric cancer patients and 156 controls. Unconditional regression (odds ratios and 95% confidence interval) was used to investigate the association of the studied polymorphisms with gastric cancer. Higher allele frequencies of R702W and 1007fs polymorphisms were observed in patients with gastric cancer compared with controls (8.53 vs 2.3 and 9.4 vs 0.7, respectively). CARD15 R702W and 1007fs polymorphisms were significantly correlated with gastric cancer incidence (p < 0.0001, p < 0.0001, respectively). No correlation was found upon analyzing the G908R single nucleotide polymorphism (SNP). Our study reports an increased susceptibility to gastric cancer in Italian populations when R702W and 1007fs polymorphisms in the coding region of CARD15 are present. The interaction between NOD-induced proinflammatory cytokines on gastric mucosa and environmental carcinogens could represent one of the mechanisms by which CARD15 polymorphisms increase the susceptibility to gastric cancer. Meta-analyses of these SNPs and further analyses of additional polymorphisms/haplotypes in NOD genes will help determine their role in carcinogenesis.

摘要

在本病例对照研究中,我们研究了 CARD15 R702W、G908R 和 1007fs 多态性在意大利胃癌患者中的潜在作用。研究人群包括 170 名胃癌患者和 156 名对照。采用条件回归(比值比和 95%置信区间)来研究研究多态性与胃癌的相关性。与对照组相比,胃癌患者的 R702W 和 1007fs 多态性等位基因频率更高(分别为 8.53%、2.3%和 9.4%、0.7%)。CARD15 R702W 和 1007fs 多态性与胃癌的发生显著相关(p<0.0001、p<0.0001)。分析 G908R 单核苷酸多态性(SNP)时未发现相关性。我们的研究报告称,在意大利人群中,当 CARD15 编码区的 R702W 和 1007fs 多态性存在时,胃癌的易感性增加。NOD 诱导的促炎细胞因子与环境致癌物在胃黏膜上的相互作用可能是 CARD15 多态性增加胃癌易感性的机制之一。对这些 SNP 的荟萃分析以及对 NOD 基因中其他多态性/单倍型的进一步分析将有助于确定它们在致癌作用中的作用。

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