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基质金属蛋白酶-8 基因型、吸烟、饮酒和感染对胃癌的影响。

Impacts of Matrix Metalloproteinase-8 Genotypes, Smoking, Alcohol Drinking, and Infection on Gastric Cancer.

机构信息

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.

Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.

出版信息

Anticancer Res. 2024 Oct;44(10):4225-4232. doi: 10.21873/anticanres.17253.

Abstract

BACKGROUND/AIM: In gastric cancer (GCa) tissues, mRNA expression of matrix metalloproteinase-8 (MMP-8) is notably reduced compared to healthy tissues. Furthermore, abnormally low or elevated serum levels of MMP-8 have been linked to a significantly poor prognosis. The involvement of MMP-8 genotypes in susceptibility to GCa remains underexplored. We aimed to assess the influence of MMP-8 genotypes on GCa susceptibility and their potential interactions with smoking, alcohol consumption, and Helicobacter pylori (H. pylori) infection.

PATIENTS AND METHODS

The study utilized polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) to analyze MMP-8 rs11225395, rs34009635, and rs35866072 genotypes in 161 GCa patients and 483 controls.

RESULTS

No statistically significant difference was detected in the distribution of genotypic (p for trend=0.3635) or allelic (p=0.1954) frequencies of MMP-8 rs11225395. Under a dominant model, combined CT+TT genotypes showed no association with GCa risk [odds ratio (OR)=0.77, 95% confidence interval (95%CI)=0.54-1.10, p=0.1852]. Similarly, no association was observed for MMP-8 rs34009635 or rs35866072. Importantly, individuals with the MMP-8 rs11225395 CC genotype demonstrated a significant increase in GCa risk when exposed to smoking (OR=4.04, 95%CI=2.28-7.16, p=0.0001), alcohol consumption (OR=2.83, 95%CI=1.64-4.89, p=0.0002), and H. pylori infection (OR=3.53, 95%CI=2.12-5.90, p=0.0001).

CONCLUSION

The findings indicate that individuals carrying the MMP-8 rs11225395 CC genotype have increased susceptibility to GCa, especially when combined with risk factors, such as smoking, alcohol consumption, and H. pylori infection. These results suggest that MMP-8 genotype-based preventive strategies, including lifestyle alterations and targeted infection treatments, may be valuable in mitigating GCa development.

摘要

背景/目的:在胃癌(GCa)组织中,与健康组织相比,基质金属蛋白酶-8(MMP-8)的 mRNA 表达明显降低。此外,血清中 MMP-8 水平异常降低或升高与预后显著不良有关。MMP-8 基因型与 GCa 易感性的关系仍未得到充分研究。我们旨在评估 MMP-8 基因型对 GCa 易感性的影响及其与吸烟、饮酒和幽门螺杆菌(H. pylori)感染的潜在相互作用。

患者和方法

本研究采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析了 161 例 GCa 患者和 483 例对照的 MMP-8 rs11225395、rs34009635 和 rs35866072 基因型。

结果

MMP-8 rs11225395 的基因型(趋势检验 p=0.3635)或等位基因(p=0.1954)频率分布无统计学差异。在显性模型下,CT+TT 基因型组合与 GCa 风险无关[比值比(OR)=0.77,95%置信区间(95%CI)=0.54-1.10,p=0.1852]。同样,MMP-8 rs34009635 或 rs35866072 也没有关联。重要的是,当暴露于吸烟、饮酒和 H. pylori 感染时,MMP-8 rs11225395 CC 基因型的个体患 GCa 的风险显著增加[OR=4.04,95%CI=2.28-7.16,p=0.0001]、OR=2.83,95%CI=1.64-4.89,p=0.0002]和 OR=3.53,95%CI=2.12-5.90,p=0.0001]。

结论

研究结果表明,携带 MMP-8 rs11225395 CC 基因型的个体对 GCa 的易感性增加,尤其是当与吸烟、饮酒和 H. pylori 感染等危险因素结合时。这些结果表明,基于 MMP-8 基因型的预防策略,包括生活方式改变和靶向感染治疗,可能有助于减轻 GCa 的发生。

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