Polymorphisms in the caspase-8 gene and the risk of lung cancer
Polymorphisms in the caspase-8 gene and the risk of lung cancer
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DOI：
10.1016/j.cancergencyto.2006.04.001
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发表时间：
2006-09-01
影响因子：
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通讯作者：
Park, Jae Yong
中科院分区：
文献类型：
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作者：
Son, Ji-Woong;Kang, Hyo-Kyung;Park, Jae Yong
Caspase-8（CASP-8）是细胞死亡受体介导的凋亡途径中的启动子，在肿瘤的发生发展中起重要作用。CASP-8基因的多态性及其单倍型可导致CASP-8表达和/或活性的改变，从而调节对肺癌的易感性。为了验证这一假设，我们研究了-678_-673delAGTAAG（-678det）和IVS 12 - 19 G-> A多态性及其单倍型与韩国人群肺癌风险的关系。在432名肺癌患者和432名年龄和性别匹配的健康对照者中测定了CASP-8基因型。CASP-8 - 678 del和IVS 12 - 19 G-> A基因型在肺癌组和对照组中的分布差异无统计学意义。然而，当病例按肿瘤组织学分类时，与IVS 12 -19 GG基因型相比，IVS 12 -19 AA基因型和IVS 12 - 19 GA + AA基因型与小细胞癌（SmCC）风险显著降低相关[校正比值比（OR）= 0.14，95%置信区间（CI）= 0.03-0.64，P = 0.01;校正OR = 0.56，95%CI = 0.33-0.96，P = 0.03]。与基因分型分析一致，与-678del-/IVS 12 - 19 G相比，研究人群中含有94% IVS 12 - 19 A等位基因的-678del-/IVS 12 - 19 A单倍型与SmCC风险显著降低相关（校正OR = 0.58，95%CI = 0.36-0.93，P = 0.023，Pc = 0.046）。这些发现表明，CASP-8基因可能有助于肺SmCC的遗传易感性。(c)2006爱思唯尔公司All rights reserved.
Caspase-8 (CASP-8) is an initiator CASP in the cell death receptor-mediated apoptotic pathway, and plays an important role in the development of cancer. Polymorphisms and their haplotypes in the CASP-8 gene can result in alterations in CASP-8 expression and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we examined the association of -678_-673delAGTAAG (-678det) and IVS12-19G -> A polymorphisms and their haplotypes with the risk of lung cancer in a Korean population. The CASP-8 genotypes were determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. The distributions of the CASP-8 -678del and IVS12-19G -> A genotypes were not significantly different between the overall lung cancer cases and the controls. When the cases were categorized by tumor histology, however, the IVS12-19 AA genotype and the combined IVS12-19 GA + AA genotype were associated with a significantly decreased risk of small cell carcinoma (SmCC) compared with the IVS12-19 GG genotype [adjusted odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.03-0.64, P = 0.01; and adjusted OR = 0.56, 95% CI = 0.33-0.96, P = 0.03, respectively]. Consistent with the genotyping analyses, the -678del-/IVS12-19A haplotype containing 94% of the IVS12-19A allele in the study population was associated with a significantly decreased risk of SmCC compared with the -678del-/IVS12-19G (adjusted OR = 0.58, 95% CI = 0.36-0.93, P = 0.023, and Pc = 0.046). These findings suggest that the CASP-8 gene may contribute to an inherited predisposition to SmCC of the lung. (c) 2006 Elsevier Inc. All rights reserved.