TIMP-3 -1296 T>C and TIMP-4 -55 T>C gene polymorphisms play a role in the susceptibility of hepatocellular carcinoma among women

• Published in: Tumor biology Vol. 35; no. 9; pp. 8999 - 9007
• Main Authors: Tsai, Hsiu-Ting, Hsieh, Ming-Ju, Chiou, Hui-Ling, Lee, Hsiang-Lin, Hsin, Min-Chieh, Liou, Yi-Sheng, Yang, Chen-Chieh, Yang, Shun-Fa, Kuo, Wu-Hsien
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.09.2014; Springer Nature B.V
• Subjects: Analysis of Variance; Asian People - genetics; Biomarkers; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Hepatocellular - ethnology; Carcinoma, Hepatocellular - genetics; Case-Control Studies; Cellular biology; Female; Gene Frequency; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genetics; Genotype; Hepatology; Humans; Linkage Disequilibrium; Liver Neoplasms - ethnology; Liver Neoplasms - genetics; Male; Middle Aged; Polymorphism; Polymorphism, Single Nucleotide; Research Article; Risk Factors; Sex Factors; Taiwan; Tissue Inhibitor of Metalloproteinase-3 - genetics; Tissue Inhibitor of Metalloproteinase-4; Tissue Inhibitor of Metalloproteinases - genetics; Womens health; Taiwan; Hepatocellular carcinoma; Single nucleotide polymorphism
• ISSN: 1010-4283; 1423-0380; 1423-0380
• DOI: 10.1007/s13277-014-2170-z

The purpose of this study was to investigate genetic impact of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724) gene polymorphisms on the susceptibility and clinicopathological characteristics of hepatocellular carcinoma (HCC). A total of 759 subjects, including 530 healthy controls and 229 patients with hepatocellular carcinoma, were recruited in this study. Allelic discrimination of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724) polymorphisms was assessed with the ABI StepOne™ Real-Time PCR System. Among women group, individuals with TC or CC alleles of TIMP-3 -1296 T>C gene polymorphism protected against HCC (AOR = 0.35, 95% confidence interval (CI) = 0.12–0.97; p  = 0.04) compared to individuals with TT alleles, after adjusting for other confounders. Also, women with TC alleles and with TC or CC alleles of TIMP-4 -55 T>C polymorphisms had a 2.52-fold risk (95%CI = 1.23–5.13; p  = 0.01) and 2.47-fold risk (95%CI = 1.26–4.87; p  = 0.008) of developing HCC compared to individuals with TT alleles, after adjusting for other confounders. There was no synergistic effect between gene polymorphism and environmental risk factors, including tobacco and alcohol consumptions and clinical statuses of HCC as well as serum expression of liver-related clinicopathological markers. In conclusion, gene polymorphisms of TIMP-3 -1296 T>C (rs9619311) and TIMP-4 -55 T>C (rs3755724) play a role in the susceptibility of HCC among Taiwan women.