Contributions of Tissue Inhibitor of Metalloproteinase-1 Genotypes to the Risk of Metastasis in Gastric Cancer.

IF 1.6 4区医学 Q4 ONCOLOGY

Anticancer research Pub Date : 2024-11-01 DOI:10.21873/anticanres.17309

Chun-Kai Fu, Hsu-Tung Lee, Jaw-Chyun Chen, Mei-Due Yang, Hsu-Chen Cheng, Mei-Chin Mong, Chia-Wen Tsai, Wen-Shin Chang, Yi-Chih Hung, DA-Tian Bau

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引用次数: 0

Abstract

Background/aim: In gastric cancer (GCa) tissues, the mRNA and protein levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) are significantly elevated compared to adjacent non-cancerous tissues. Moreover, the abnormal up-regulation of TIMP-1 has been associated with a poor prognosis. However, the role of TIMP-1 genotypes in susceptibility to GCa has seldom been investigated. This study aimed to evaluate the influence of TIMP-1 genotypes on GCa susceptibility and their potential interactions with clinico-pathological factors, including age, sex, body mass index, smoking, alcohol consumption, Helicobacter pylori (H. pylori) infection, and metastasis status.

Materials and methods: TIMP-1 rs4898, rs6609533, and rs2070584 genotypes were analyzed in 161 patients with GCa and 483 non-cancer control subjects from a Taiwanese population using PCR-RFLP methodology and direct sequencing.

Results: The genotypic (p for trend=0.1987) and allelic (p=0.0733) frequencies of TIMP-1 rs4898 did not differ significantly between GCa cases and controls. Under the dominant model, combined CT+CC genotypes were not associated with GCa risk [odds ratio (OR)=0.74, 95% confidence interval (95%CI)=0.51-1.07, p=0.1272]. Similarly, no significant association was found for TIMP-1 rs6609533 or rs2070584 polymorphisms. Importantly, patients with GCa carrying the TIMP-1 rs4898 TT genotype exhibited a significantly enhanced risk of GCa when they had smoking (p=0.0140) and alcohol drinking habits (p=0.0011). Furthermore, the CC genotype of TIMP-1 rs4898 was linked to a lower risk of distant metastasis.

Conclusion: The TIMP-1 rs4898 CC genotype may serve as a prognostic biomarker and could inform lifestyle modifications aimed at GCa prevention. Validation of TIMP-1 genotypic profile in diverse populations is warranted.

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组织金属蛋白酶抑制剂-1基因型对胃癌转移风险的影响

背景/目的：在胃癌（GCa）组织中，与邻近的非癌组织相比，组织金属蛋白酶抑制剂-1（TIMP-1）的 mRNA 和蛋白水平明显升高。此外，TIMP-1 的异常上调与预后不良有关。然而，TIMP-1基因型在GCa易感性中的作用却鲜有研究。本研究旨在评估 TIMP-1 基因型对 GCa 易感性的影响及其与年龄、性别、体重指数、吸烟、饮酒、幽门螺杆菌（H. pylori）感染和转移状态等临床病理因素的潜在相互作用：采用PCR-RFLP方法和直接测序法分析了台湾人群中161名GCa患者和483名非癌症对照者的TIMP-1 rs4898、rs6609533和rs2070584基因型：结果：TIMP-1 rs4898的基因型频率（趋势p=0.1987）和等位基因频率（p=0.0733）在GCa病例和对照组之间没有显著差异。在显性模型下，CT+CC 组合基因型与 GCa 风险无关[几率比（OR）=0.74，95% 置信区间（95%CI）=0.51-1.07，p=0.1272]。同样，TIMP-1 rs6609533 或 rs2070584 多态性也没有发现明显的关联。重要的是，携带 TIMP-1 rs4898 TT 基因型的 GCa 患者在有吸烟（p=0.0140）和饮酒习惯（p=0.0011）时，患 GCa 的风险明显增加。此外，TIMP-1 rs4898的CC基因型与较低的远处转移风险有关：结论：TIMP-1 rs4898 CC 基因型可作为一种预后生物标志物，并可为旨在预防 GCa 的生活方式调整提供依据。有必要在不同人群中验证 TIMP-1 基因型特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Anticancer research 医学-肿瘤学

CiteScore

3.70

自引率

10.00%

发文量

566

审稿时长

2 months

期刊介绍： ANTICANCER RESEARCH is an independent international peer-reviewed journal devoted to the rapid publication of high quality original articles and reviews on all aspects of experimental and clinical oncology. Prompt evaluation of all submitted articles in confidence and rapid publication within 1-2 months of acceptance are guaranteed. ANTICANCER RESEARCH was established in 1981 and is published monthly (bimonthly until the end of 2008). Each annual volume contains twelve issues and index. Each issue may be divided into three parts (A: Reviews, B: Experimental studies, and C: Clinical and Epidemiological studies). Special issues, presenting the proceedings of meetings or groups of papers on topics of significant progress, will also be included in each volume. There is no limitation to the number of pages per issue.