Anticancer research · 2026
Insights From Matrix Metalloproteinase-2 Genotypes to Decipher the Genetic Architecture of Bladder Cancer Risk.
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Liao Cheng-Hsi, Chang Wen-Shin, Chang Shu-Yu, Wang Yun-Chi, Chen Jaw-Chyun, Shih Hou-Yu, Chang Chao-Hsiang, Chen Wen-Chi, Bau DA-Tian, Tsai Chia-Wen
Аннотация
BACKGROUND/AIM: Bladder cancer (BLCA) is a prevalent malignancy globally, particularly in Taiwan, where its incidence continues to rise. While environmental exposures such as smoking play critical roles in BLCA etiology, genetic predispositions also contribute significantly. Matrix metalloproteinase-2 (MMP-2), a key enzyme involved in extracellular matrix remodeling, has been implicated in BLCA progression. This study investigated the associations of two promoter polymorphisms in the MMP-2 gene, rs243865 and rs2285053, with BLCA susceptibility in a Taiwanese population.
PATIENTS AND METHODS: A case-control study was conducted involving 375 BLCA patients and 375 cancer-free controls matched by age and sex. Genotyping was performed using PCR-RFLP, and associations with BLCA risk were evaluated using logistic regression, adjusting for confounders. Stratified analyses were performed based on demographic and clinical parameters.
RESULTS: No significant association was observed between rs243865 and overall BLCA risk (OR=1.34, 95%CI=0.96-1.86, p=0.0953). In contrast, rs2285053 showed a significant allelic association with BLCA (OR=1.33, 95%CI=1.04-1.69, p=0.0263). Stratified analysis revealed that younger individuals (≤55 years) carrying the CT genotype of rs243865 had a significantly elevated BLCA risk (OR=2.48, 95%CI=1.39-4.42, p=0.0028). Among smokers, both CT and TT genotypes of rs2285053 were associated with increased risk (OR=1.68 and 4.01, p=0.0214 and 0.0045). Additionally, rs243865 TT genotype was associated with muscle-invasive BLCA (OR=3.68, 95%CI=1.96-6.91, p=0.0001).
CONCLUSION: MMP-2 rs2285053 and, to a lesser extent, rs243865 polymorphisms may influence BLCA susceptibility and aggressiveness, particularly in the context of age and smoking. These variants may serve as potential biomarkers for personalized risk assessment, pending validation in larger, multiethnic cohorts.
PATIENTS AND METHODS: A case-control study was conducted involving 375 BLCA patients and 375 cancer-free controls matched by age and sex. Genotyping was performed using PCR-RFLP, and associations with BLCA risk were evaluated using logistic regression, adjusting for confounders. Stratified analyses were performed based on demographic and clinical parameters.
RESULTS: No significant association was observed between rs243865 and overall BLCA risk (OR=1.34, 95%CI=0.96-1.86, p=0.0953). In contrast, rs2285053 showed a significant allelic association with BLCA (OR=1.33, 95%CI=1.04-1.69, p=0.0263). Stratified analysis revealed that younger individuals (≤55 years) carrying the CT genotype of rs243865 had a significantly elevated BLCA risk (OR=2.48, 95%CI=1.39-4.42, p=0.0028). Among smokers, both CT and TT genotypes of rs2285053 were associated with increased risk (OR=1.68 and 4.01, p=0.0214 and 0.0045). Additionally, rs243865 TT genotype was associated with muscle-invasive BLCA (OR=3.68, 95%CI=1.96-6.91, p=0.0001).
CONCLUSION: MMP-2 rs2285053 and, to a lesser extent, rs243865 polymorphisms may influence BLCA susceptibility and aggressiveness, particularly in the context of age and smoking. These variants may serve as potential biomarkers for personalized risk assessment, pending validation in larger, multiethnic cohorts.