Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2012-09, Vol.61 (9), p.1433-1439
• Main Authors: Ren, Shan, Lu, Junfeng, Du, Xiaofei, Huang, Yanxiang, Ma, Lina, Huo, Honglei, Chen, Xinyue, Wei, Lai
• Format: Article
• Language: English
• Subjects: Antibodies; Antigens; Antineoplastic agents; Biological and medical sciences; Cancer Research; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - virology; Case-Control Studies; Chronic infection; Cytokines; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Frequency; Gene polymorphism; Genetic diversity; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic - genetics; Hepatitis B, Chronic - immunology; Hepatitis C; Hepatocellular carcinoma; Hospitals; Human viral diseases; Humans; Immunology; Immunotherapy; Infections; Infectious diseases; Interferon; Interferons; Interleukins - blood; Interleukins - genetics; Liver cancer; Liver diseases; Liver Neoplasms - genetics; Liver Neoplasms - immunology; Liver Neoplasms - virology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Oncology; Original; Original Article; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Single Nucleotide; Risk Factors; Single-nucleotide polymorphism; Statistical analysis; Tumors; Viral diseases; Viral hepatitis
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-012-1203-y

To evaluate the role of host IL28B (interleukin 28B; interferon lambda 3) single nucleotide polymorphisms (SNPs) in predicting hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, three SNPs in the IL28B gene (rs12979860C/T, rs8099917G/T and rs12980275G/A) were examined in 330 subjects (including 154 HBV-related HCC patients, 86 non-HCC patients with chronic hepatitis B (CHB), 43 HBV self-limited infections and 47 healthy controls). Notably, the frequency of CC homozygosity was 91.5% in healthy controls and 72.9% in CHB, the difference being statistically significant ( χ 2  = 6.40, P  = 0.01). The statistically difference was seen between healthy controls (91.5%) and HCC (74.7%) ( χ 2  = 6.05, P  = 0.01). However, this significant finding was not seen between HBV self-limited and healthy controls. Carriers of the minor T allele in rs12979860 had a higher risk of HCC compared with non-carriers ( χ 2  = 4.44, P  = 0.04). Haplotype analyses revealed significant association between haplotype C–T–A and healthy controls, but not with the HCC group (96.6 vs. 82.0%, χ 2  = 6.08, P  = 0.01). Analyses of genotype combination and gene–gene interaction showed that there was a positive interaction between rs12979860 and rs12980275, with an OR rate of 11.79 (likelihood test, P  = 0.04). Our results suggest that the IL28B rs12979860 C/T polymorphism might affect susceptibility to the chronic HBV infection and progression of HCC. Of note, the T allele and non-CC genotypes have strong predictive effect of increasing susceptibility of chronic HBV infection and HCC.