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Genetic predisposition of nuclear factor-kappa B (NF-κB)-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 ofNFKB1encoding NF-κB1 andNFKBIAencoding 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 ofNFKBIAwere more prevalent in HCC patients than in the healthy controls.NFKBIA−826CT andNFKBIA−881AG allelic carriages were more prevalent in HCC patients than in the non-HCC subjects with HBV infection. The estimated haplotype frequency ofNFKBIApromoter −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 andNFKBIA−881AG allelic carriages were only associated with HCC risk in the subjects with HBV genotype C. The association ofNFKBIA−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 inNFKBIApromoter were associated with hepatocarcinogenesis.NFKBIA−826T and −881AG were associated with the risk of HCC in the subjects infected with HBV genotype C.

IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C