IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C.
Genetic predisposition of nuclear factor-kappa B (NF-kappaB)-signaling pathways linking inflammation to hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) remains unresolved. We conducted a case-control study to determine the associations of the polymorphisms within the promoter regions of NFKB1 encoding NF-kappaB1 and NFKBIA encoding IkappaBalpha with the development of HCC. A total of 404 healthy controls, 482 non-HCC subjects with HBV infection and 202 patients with HCC were included. NFKB1 -94ATTG2 allele and GG allele in the 3'-untranslated region of NFKBIA were more prevalent in HCC patients than in the healthy controls. NFKBIA -826CT and NFKBIA -881AG allelic carriages were more prevalent in HCC patients than in the non-HCC subjects with HBV infection. The estimated haplotype frequency of NFKBIA promoter -881G-826T-519C was significantly higher in the patients with HCC than in the HBV-infected subjects without HCC (odds ratio = 3.142, P = 0.002). As compared with the HBV-infected subjects without HCC, NFKBIA -826 T and NFKBIA -881AG allelic carriages were only associated with HCC risk in the subjects with HBV genotype C. The association of NFKBIA -881AG allelic carriage with HCC risk was not affected by liver cirrhosis (LC) status, alanine aminotransferase level and hepatitis B e antigen status. By multivariate regression analysis, NFKB1 -94ATTG2, NFKBIA -826T, NFKBIA -881AG and HBV genotype C were independently associated with an increased risk of HCC. In conclusion, NFKB1 -94ATTG2 allele and haplotype -881G-826T-519C in NFKBIA promoter were associated with hepatocarcinogenesis. NFKBIA -826T and -881AG were associated with the risk of HCC in the subjects infected with HBV genotype C.
He
Yongchao
Y
Department of Epidemiology, the 1st Affiliated Hospital, Second Military Medical University, Shanghai 200433, People's Republic of China.
Zhang
Hongwei
H
Yin
Jianhua
J
Xie
Jiaxin
J
Tan
Xiaojie
X
Liu
Shijian
S
Zhang
Qian
Q
Li
Chengzhong
C
Zhao
Jun
J
Wang
Hongyang
H
Cao
Guangwen
G
D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006509:Hepatitis B / Q000150:complications* / Q000235:genetics; D006513:Hepatitis B e Antigens / Q000235:genetics; D006515:Hepatitis B virus; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D052002:NF-kappa B p50 Subunit / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D006513:Hepatitis B e Antigens; D020672:I-kappa B Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha