Tumor necrosis factor-alpha 308.2 polymorphism is associated with advanced hepatic fibrosis and higher risk for hepatocellular carcinoma.
OBJECTIVE
Host genetic factor and hepatic fibrosis may predispose to risk for hepatocellular carcinoma (HCC). This study aimed to assess the association between tumor necrosis factor (TNF) alpha polymorphism and hepatic fibrosis, and risk for HCC.


METHODS
One hundred eight pairs of gender-matched and age-matched patients with HCC and unrelated healthy controls were genotyped for TNF308.2 and TNF238.2 alleles with polymerase chain reaction and direct sequencing.


RESULTS
The frequency of TNF308.1/TNF308.2 genotype in cases was higher than that in controls [odds ratio (OR) = 4.37]. Multivariate analysis indicated that TNF308.2 allele (OR = 3.23), hepatitis B surface antigen (OR = 17.17), and antibodies to hepatitis C virus (OR = 45.52) were independent risk factors for HCC. Surrogate markers for significant fibrosis implied that cases with the TNF308.2 allele have more advanced liver fibrosis. Moreover, multivariate analysis indicated that cirrhosis with Child-Pugh grade C, low serum albumin, and low platelet count were independent risk factors for carrying the TNF308.2 allele.


CONCLUSIONS
TNF308.2 allele carriage and chronic hepatitis B virus/hepatitis C virus infection are independent risk factors for HCC. Carriage of the TNF308.2 allele correlates with disease severity and hepatic fibrosis, which may contribute to a higher risk for HCC.
Jeng
Jen-Eing
JE
Department of Clinical Laboratory, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Tsai
Jung-Fa
JF
Chuang
Lee-Yea
LY
Ho
Mei-Shang
MS
Lin
Zu-Yau
ZY
Hsieh
Min-Yuh
MY
Chen
Shin-Chern
SC
Chuang
Wan-Lung
WL
Wang
Liang-Yen
LY
Yu
Ming-Lung
ML
Dai
Chia-Yen
CY
Chang
Jan-Gowth
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha