Anticancer research · 2025
Elucidating the Genetic Contribution to Nasopharyngeal Carcinoma Risk Through Matrix Metalloproteinase-11 (MMP-11) Genotypic Analysis.
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Hsu Shih-Wei, Hsu Che-Lun, Shih Hou-Yu, Chen Kai-Yuan, Wang Yun-Chi, Tsai Chia-Wen, Hsia Te-Chun, Bau DA-Tian, Chang Wen-Shin
Аннотация
BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC) is a distinct malignancy of epithelial origin with multifactorial etiology involving Epstein-Barr virus, genetic susceptibility, and environmental exposures. MMP-11, a matrix metalloproteinase implicated in extracellular matrix remodeling and cancer progression, is overexpressed in NPC tissues; however, its genetic role in NPC remains unexplored.
MATERIALS AND METHODS: This case-control study investigated four MMP-11 single nucleotide polymorphisms (SNPs), rs738791, rs2267029, rs738792, and rs28382575, in 208 patients with NPC and 416 matched cancer-free controls from a Taiwanese cohort. Genotypic distributions were tested for Hardy-Weinberg equilibrium, and logistic regression was used to evaluate associations with NPC risk. Stratified analyses assessed gene-environment interactions with smoking, alcohol drinking, and betel quid chewing.
RESULTS: No significant associations were found between any of the four MMP-11 genotypes and NPC risk under co-dominant or dominant models (all p>0.05). Allelic analysis further supported the lack of independent associations. However, significant gene-environment interactions were observed. The rs2267029 variant genotypes (AG+AA) conferred increased NPC risk among alcohol drinkers [odds ratio (OR)=1.90, 95% confidence interval (CI)=1.09-3.30, p=0.0326] and betel quid chewers (OR=2.50, 95%CI=1.41-4.43, p=0.0025). Similarly, rs738792 variant genotypes (CT+CC) showed a strong interaction with betel quid chewing (OR=2.15, 95%CI=1.22-3.80, p=0.0119). A borderline interaction was noted between rs738791 and smoking (OR=1.80, 95%CI=1.00-3.20, p=0.0645).
CONCLUSION: While MMP-11 polymorphisms alone do not independently influence NPC susceptibility, their interaction with environmental risk factors may modulate NPC risk. These findings suggest potential roles for MMP-11 genotypes in NPC pathogenesis via gene-environment interplay and merit further investigation in diverse populations.
MATERIALS AND METHODS: This case-control study investigated four MMP-11 single nucleotide polymorphisms (SNPs), rs738791, rs2267029, rs738792, and rs28382575, in 208 patients with NPC and 416 matched cancer-free controls from a Taiwanese cohort. Genotypic distributions were tested for Hardy-Weinberg equilibrium, and logistic regression was used to evaluate associations with NPC risk. Stratified analyses assessed gene-environment interactions with smoking, alcohol drinking, and betel quid chewing.
RESULTS: No significant associations were found between any of the four MMP-11 genotypes and NPC risk under co-dominant or dominant models (all p>0.05). Allelic analysis further supported the lack of independent associations. However, significant gene-environment interactions were observed. The rs2267029 variant genotypes (AG+AA) conferred increased NPC risk among alcohol drinkers [odds ratio (OR)=1.90, 95% confidence interval (CI)=1.09-3.30, p=0.0326] and betel quid chewers (OR=2.50, 95%CI=1.41-4.43, p=0.0025). Similarly, rs738792 variant genotypes (CT+CC) showed a strong interaction with betel quid chewing (OR=2.15, 95%CI=1.22-3.80, p=0.0119). A borderline interaction was noted between rs738791 and smoking (OR=1.80, 95%CI=1.00-3.20, p=0.0645).
CONCLUSION: While MMP-11 polymorphisms alone do not independently influence NPC susceptibility, their interaction with environmental risk factors may modulate NPC risk. These findings suggest potential roles for MMP-11 genotypes in NPC pathogenesis via gene-environment interplay and merit further investigation in diverse populations.