Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea

• Published in: World journal of gastroenterology : WJG Vol. 21; no. 46; pp. 13064 - 13072
• Main Authors: Shin, Suk Pyo, Kim, Nam Keun, Kim, Ju Hwan, Lee, Ju Ho, Kim, Jung Oh, Cho, Sung Hwan, Park, Hana, Kim, Mi Na, Rim, Kyu Sung, Hwang, Seong Gyu
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 14.12.2015
• Subjects: Adult; Aged; Asian Continental Ancestry Group - genetics; Carcinoma, Hepatocellular - ethnology; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Case Control Study; Case-Control Studies; Chi-Square Distribution; factor-alpha;Polymorphism;Single; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Haplotypes; Humans; Kaplan-Meier Estimate; Liver Neoplasms - ethnology; Liver Neoplasms - genetics; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Logistic Models; Male; Middle Aged; necrosis; Neoplasm Staging; Odds Ratio; Phenotype; Polymorphism, Genetic; Proportional Hazards Models; Republic of Korea - epidemiology; Risk Factors; Tumor; Tumor Necrosis Factor-alpha - genetics; Hepatocellular; Tumor necrosis factor-alpha; Carcinoma; Single nucleotide; Polymorphism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v21.i46.13064

AIM: To investigate associations between the tumor necrosis factor alpha(TNF-α)-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A polymorphisms and HCC in Korea.METHODS: Hepatocellular carcinoma(HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms,which are TNF-α-1031 T>C,-863 C>A,-857 C>T,-308 G>A,and-238 G>A. The TNF-α genotype frequencies,genotype combinations and haplotypes were analyzed to disclose the association with HCC.RESULTS: None of the TNF-α polymorphisms was significantly associated with HCC. However,nine genotype combinations had associations with increased likelihood of HCC. Among them,TNF-α-1031/-857/-238 TT/CC/GA(AOR = 18.849,95%CI: 2.203-161.246,P = 0.007),TNF-α-1031/-308/-238 TT/GG/GA(AOR = 26.956,95%CI: 3.071-236.584,P = 0.003),and TNF-α-1031/-238 TT/GA(AOR = 21.576,95%CI: 2.581-180.394,P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α-1031/-863/-857/-308/-238 T-C-C-G-A(OR = 25.824,95%CI: 1.491-447.223,P = 0.0005),TNF-α-1031/-857/-308/-238 T-C-G-A(OR = 12.059,95%CI: 2.747-52.950,P < 0.0001),TNF-α-1031/-857/-238 T-C-A(OR = 10.696,95%CI: 2.428-47.110,P = 0.0001),TNF-α-1031/-308/-238 T-G-A(OR = 7.556,95%CI: 2.173-26.280,P = 0.0002) and TNF-α-1031/-238 T-A(OR = 10.865,95%CI: 2.473-47.740,P = 0.0001). Moreover,HCC Okuda stage Ⅲ cases with the TNF-α-1031 CC genotype had better survival than those with the TT genotype(AOR = 5.795,95%CI: 1.145-29.323). CONCLUSION: Although no single TNF-α polymorphism is associated with HCC in this study,some TNF-α genotype combinations and haplotypes are associated with HCC. In addition,HCC Okuda stage Ⅲ cases with the TNF-α-1031 TT genotype may have a better prognosis than those with the CC genotype.