Genetic polymorphism of interleukin-16 influences susceptibility to HBV-related hepatocellular carcinoma in a Chinese population.

Aim: Interleukin-16 (IL16) as a multifunctional cytokine, plays a key role in inflammatory and autoimmune diseases as well as tumour growth and progression. Recently, genetic polymorphisms of IL16 have been reported to be associated with susceptibility to a range of cancers. This study was undertaken to investigate the IL16 gene polymorphisms and determine whether these genetic factors are related to the occurrence of hepatocellular carcinoma (HCC) in a Chinese population.

Methods: We analyzed three polymorphisms of the IL16 gene (rs11556218T/G, rs4072111C/T and rs4778889T/C) in 206 patients with HBV-related HCC, 270 chronic hepatitis B patients and 264 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and DNA sequencing technology.

Results: IL16 polymorphisms were not associated with risk of HCC when compared with healthy controls. However, IL16 polymorphisms were significantly associated with susceptibility to HBV-related HCC when using chronic hepatitis B patients as controls. The rs11556218T/G TG and GG genotypes were associated with significantly increased risk of HBV-related HCC compared with the TT genotype (OR = 1.96 and OR = 3.33). The data also revealed that subjects with the G allele appeared to have higher susceptibility to HBV-related HCC than those with the T allele (OR = 2.10). Under the dominant model genotype TG+GG appeared to be associated with an increased risk of HBV-related HCC (OR = 2.18). The rs4072111C/T TT genotype was associated with a significantly increased risk of HBV-related HCC compared with the CC genotype (OR = 6.67). Polymorphisms of the IL16 gene were significantly associated with susceptibility to chronic hepatitis B when using healthy subjects as controls. The rs11556218T/G TG and GG genotypes were associated with significantly decreased risk of chronic hepatitis B compared with the TT genotype (OR = 0.49 and OR = 0.29). The data also revealed that subjects with the G allele appeared to have lower susceptibility to chronic hepatitis B than those with the T allele (OR = 0.46). Under the dominant model genotype TG + GG appeared to have lower susceptibility to chronic hepatitis B (OR = 0.44).

Conclusions: This study showed that the genotypes and allele of IL16 SNPs were associated with chronic HBV infection and HCC. However, further investigation with a larger sample size and haplotype analysis with other SNPs may be required to validate the genetic effects of the IL16 polymorphisms on chronic HBV infection and HCC.