title: Association between hepatocellular carcinoma and tumor necrosis factor alpha polymorphisms in South Korea.
abstract: OBJECTIVE
  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 157 HCC 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Suk Pyo
authors.initials: SP
authors.lastname: Shin
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Ju Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Jung Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Park
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Mi Na
authors.initials: MN
authors.lastname: Kim
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Kyu Sung
authors.initials: KS
authors.lastname: Rim
authors.affiliation: Suk Pyo Shin, Ju Hwan Kim, Ju Ho Lee, Hana Park, Kyu Sung Rim, Seong Gyu Hwang, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam 463-712, South Korea.
authors.forename: Seong Gyu
authors.initials: SG
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D056910:Republic of Korea / Q000453:epidemiology; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Carcinoma; Hepatocellular; Polymorphism; Single nucleotide; Tumor necrosis factor-alpha