Prognostic role of interleukin-1β gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer
Prognostic role of interleukin-1β gene and interleukin-1 receptor antagonist gene polymorphisms in patients with advanced gastric cancer
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DOI：
10.1200/jco.2005.02.345
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发表时间：
2005-04-01
影响因子：
45.3
通讯作者：
Magnani, M
中科院分区：
文献类型：
--
作者：
Graziano, F;Ruzzo, A;Magnani, M
目的白细胞介素1 β 0（IL-1 B）和白细胞介素1受体拮抗剂（IL-1 R N）的高比值是不利的促炎状态的基础。此外，它似乎还参与癌症恶病质、肿瘤血管生成和转移的机制。IL-1B基因的两个单核苷酸多态性（IL-1B-511 C/T、IL-1B-31 T/C）和IL-RN基因的可变数目串联重复多态性（IL-IRNlong/2）可提高两种细胞因子的循环水平。IL-1B/1 L-1 RN基因型的预后作用进行了调查，在复发和转移性胃癌患者接受姑息性chemotherapy.Patients和方法姑息性chemotherapy治疗前，123例前瞻性入组患者提供外周血样本的DNA提取。结果42例患者为野生型基因型（IL-1 RNlong/long，IL-1B-511 C/C，IL-1B-31 T/7; A组）。45例患者表现出IL-1 IRN 2多态性，7例患者具有野生型IL-1 B基因型，38例患者具有IL-1 B-511 C/T和/或IL-1 B-31 T/C多态性（B组）。其余36例患者表现为野生型IL-1 RN，具有IL-1B 511 C/T和/或IL-1B-37 T/C多态性（C组）。A组和B组患者的中位无进展生存期（PFS）分别为25和26周，中位总生存期（OS）分别为42和43周。C组患者的PFS（中位数，16周）和OS（中位数，28周）比A组（PFS P = 0.006; OS P = 0.0001）和B组患者（PFS P = 0.01; OS P = 0.0001）差。长/T/C单倍型在PFS缩短（P =.001）和OS缩短（P =.0005）的患者中占主导地位。结论在进展期胃癌患者中，IL-1B多态性与野生型IL-7 RN基因型相结合对预后有不利影响。这些结果值得进一步研究重组IL-RN的潜在抗癌活性。
Purpose A high interleukin-1 beta 0 (IL-1 B) and interleukin-1 receptor antagonist (IL-RN) ratio underlies an unfavorable proinflammatory status. Also, it seems to be involved in the mechanisms of cancer cachexia and tumor angiogenesis and metastasis. Two single nucleotide polymorphisms in IL-1B gene (IL-1B-511C/T,IL-1B-31T/C) and a variable number of tandem repeat polymorphisms in IL-RN gene (IL-IRNlong/2) enhance the circulating levels of the two cytokines. The prognostic role of IL-1B/1L-1RN genotypes was investigated in patients with relapsed and metastatic gastric cancer treated with palliative chemotherapy.Patients and Methods Before starting palliative chemotherapy, 123 prospectively enrolled patients supplied peripheral-blood samples for DNA extraction. Survival data were analyzed according to IL-IRN/IL-1B genotypes.Results Forty-two patients showed wild-type genotypes (IL-1RNlong/long, IL-1B-511C/C, and IL-IB-31T/7; group A). Forty-five patients showed the IL-IRN2 polymorphism, with wild-type IL-1B genotypes in seven patients and with IL-1B-511C/T and/or IL-1B-31T/C polymorphisms in 38 patients (group B). The remaining 36 patients demonstrated wild-type IL-1RN, with IL-1B511C/T and/or IL-1B-37T/C polymorphisms (group C). In group A and B patients, the median progression-free survival (PFS) was 25 and 26 weeks, respectively, and median overall survival (OS) was 42 and 43 weeks, respectively. Group C patients showed worse PFS (median, 16 weeks) and OS (median, 28 weeks) than group A (P =.006 for PFS; P =.0001 for OS) and group B patients (P =.01 for PFS; P =.0001 for OS). The long/T/C haplotype was overrepresented in patients with shortened PFS (P =.001) and OS (P =.0005).Conclusion In patients with advanced gastric cancer, IL-1B polymorphisms showed adverse prognostic influence when coupled with wild-type IL-7RN genotype. These findings deserve further investigation for potential anticancer activity of recombinant IL-RN.