Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.
Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
Anticancer Res. 2024 Oct;44(10):4225-4232. doi: 10.21873/anticanres.17253.
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.
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.
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).
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.
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。
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。
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]。
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。