Abstract
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.
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Acknowledgments
We are grateful to all the subjects who participated in this study. This work was supported by grants from the National Eleventh Five-year Science and Technology Major Projects, China (grant number 2008ZX10002-013), and the National Twelfth Five-year Science and Technology Major Projects, China (grant number 2012ZX10002-003).
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Shan Ren, Junfeng Lu and Xiaofei Du contributed equally to this work.
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Ren, S., Lu, J., Du, X. et al. Genetic variation in IL28B is associated with the development of hepatitis B-related hepatocellular carcinoma. Cancer Immunol Immunother 61, 1433–1439 (2012). https://doi.org/10.1007/s00262-012-1203-y
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DOI: https://doi.org/10.1007/s00262-012-1203-y