Increased risk of developing hepatocellular carcinoma associated with carriage of the TNF2 allele of the -308 tumor necrosis factor-alpha promoter gene.
OBJECTIVE
Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-alpha at position -308 of the promoter region, which includes TNF1 (-308G) and TNF2 (-308A) alleles, has been found to be associated with susceptibility to various types of cancer. We conducted a study to evaluate the association between this polymorphism and hepatocellular carcinoma (HCC).


METHODS
We recruited 74 HCC patients and 289 healthy controls, and determined their -308 TNF-alpha promoter genotypes through polymerase chain reaction followed by electrophoresis.


RESULTS
Carriage of the TNF2 allele was associated with an increased risk of HCC (odds ratio [OR] = 3.5; 95% confidence interval [CI]:[2.1, 6.0]), and a trend toward a significant increase in the risk of developing HCC was observed from TNF1/TNF1, TNF1/TNF2, to TNF2/TNF2 genotypes (p < 0.01). After adjustment for gender, age, and markers of hepatitis B and C, the OR of developing HCC associated with TNF2 allele carriage was 5.3 (95% CI: [2.3, 12.1]; p < 0.01)


CONCLUSIONS
Carriage of the TNF2 allele is a significant predictor of HCC independent of hepatitis B and C, and therefore it may be used as a biomarker for susceptibility to HCC.
Department of Radiation Oncology, Sin-Lau Christian Hospital, Tainan, Taiwan.
Sheng-Yow
SY
Ho
Ying-Jan
YJ
Wang
Hen-Li
HL
Chen
Chih-Hung
CH
Chen
Chih-Jen
CJ
Chang
Po-Jen
PJ
Wang
Helen H W
HH
Chen
How-Ran
HR
Guo
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha