title: Tumor Necrosis Factor-α Genotypes Are Associated with Hepatocellular Carcinoma Risk in Taiwanese Males, Smokers and Alcohol Drinkers.
abstract: OBJECTIVE
  Hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, has high prevalence and mortality rates in Taiwan. Tumor necrosis factor-α (TNFα), an important proinflammatory cytokine, is involved in multiple physiological and pathogenic phenomena that lead to the destruction and dysregulation of tissues. The present study aimed to evaluate the contribution of TNFA genotype, together with cigarette smoking and alcohol drinking lifestyle to the risk of HCC.
  
  
  METHODS
  In this hospital-based case-control study, association of TNFA single-nucleotide polymorphisms -1031T/C, -863C/A, -857T/C, -308G/A and +489A/G, with HCC risk were examined in 298 patients with HCC and 889 age- and gender-matched healthy controls.
  
  
  RESULTS
  The percentages of AA, AG and GG TNFA -308G/A were 6.4%, 18.1% and 75.5% in the HCC patient group and 2.0%, 16.0% and 82.0% in the non-cancer control group, respectively. The AA and AG genotypes were associated with 3.42- and 1.23-fold higher odds of HCC than the GG genotype (95% confidence interval=1.76-6.63 and 0.87-1.74, respectively). No such significant difference was found for other polymorphic sites. We further stratified the populations by gender, cigarette smoking and alcohol drinking status to investigate their combined contributions with TNFA -308G/A genotype to HCC risk. The results showed that the AA and AG genotypes of TNFA -308G/A increased HCC susceptibility which was obvious among males, smokers, and alcohol drinkers, but not females, non-smokers, or non-drinkers (p=0.0003, 0.0003, 0.0014, 0.6127, 0.7442 and 0.3010, respectively).
  
  
  CONCLUSIONS
  Our results suggest that the AA and AG polymorphism of TNFA -308G/A genotypes associated with HCC risk in Taiwan, particularly among males, smokers and alcohol drinkers.
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C. Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Mei-Due
authors.initials: MD
authors.lastname: Yang
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chin-Mu
authors.initials: CM
authors.lastname: Hsu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Te-Cheng
authors.initials: TC
authors.lastname: Yueh
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Yi-Liang
authors.initials: YL
authors.lastname: Lai
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chin-Liang
authors.initials: CL
authors.lastname: Chuang
authors.affiliation: Taichung Armed Forces General Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Shou-Cheng
authors.initials: SC
authors.lastname: Wang
authors.affiliation: Department of Surgery, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Hong-Xue
authors.initials: HX
authors.lastname: Ji
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Chieh-Lun
authors.initials: CL
authors.lastname: Hsiao
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
authors.forename: Cheng-Nan
authors.initials: CN
authors.lastname: Wu
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C. datian@mail.cmuh.org.tw artbau2@gmail.com.
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Alcohol drinking; TNFα; genotype; hepatocellular carcinoma; polymorphism; smoking