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

• Published in: Anticancer research Vol. 44; no. 11; pp. 4833 - 4841
• Main Authors: FU, CHUN-KAI, LEE, HSU-TUNG, CHEN, JAW-CHYUN, YANG, MEI-DUE, CHENG, HSU-CHEN, MONG, MEI-CHIN, TSAI, CHIA-WEN, CHANG, WEN-SHIN, HUNG, YI-CHIH, BAU, DA-TIAN
• Format: Journal Article
• Language: English
• Published: Greece International Institute of Anticancer Research 01.11.2024
• Subjects: Age; Aged; Alcohol; Biomarkers; Body mass index; Body size; Cancer; Case-Control Studies; Confidence intervals; Drinking behavior; Female; Gastric cancer; Gender differences; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Genotypes; Health care; Helicobacter Infections - genetics; Helicobacter pylori; Humans; Infections; Inhibitors; Male; Medical prognosis; Metalloproteinase; Metastases; Metastasis; Middle Aged; mRNA; Neoplasm Metastasis; Polymorphism, Single Nucleotide; Restriction fragment length polymorphism; Risk; Risk Factors; Smoking; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Taiwan - epidemiology; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Taiwan; Asia; single nucleotide polymorphism; Gastric cancer; tissue inhibitor of metalloproteinase-1 (TIMP-1); Taiwan; genotype
• ISSN: 0250-7005; 1791-7530; 1791-7530
• DOI: 10.21873/anticanres.17309

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. 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. 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. 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.