title: Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population.
abstract: OBJECTIVE
  Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual's susceptibility to hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with HBV-related HCC in a Chinese population.
  
  
  METHODS
  The +114T/G and -384T/G polymorphisms in the IL-2 gene were examined in 115 cases of chronic hepatitis B (CHB), 67 cases of HBV-related liver cirrhosis (LC), 107 cases of HBV-related HCC, and 105 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  We found that there were significant differences in the genotype and allele frequencies of the IL-2 gene +114T/G polymorphism between the HBV-related HCC patients and the healthy controls. The +114 TG and GG genotypes were associated with a significant increased HCC risk as compared with the TT genotype (OR=1.988, 95% CI, 1.034-3.480, P=0.009 for TG genotype, and OR=1.975, 95% CI, 1.012-3.341, P=0.013 for GG genotype, respectively). The +114 G allele was correlated with a significant increased HCC risk as compared with the T allele (OR=1.423, 95% CI, 1.023-1.975, P=0.031). In addition, we found significant decreased serum IL-2 in HBV-related HCC patients (288.6±177.1ng/L) compared with healthy controls (238.2±136.7ng/L) (t=2.32, P=0.021). Genotypes carrying the +114 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in HBV-related HCC patients.
  
  
  CONCLUSIONS
  The results suggested that the IL-2 +114T/G polymorphism may contribute to increased HBV-related HCC risk through regulating the serum IL-2 levels. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Qiliu
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Xianjun
authors.initials: X
authors.lastname: Lao
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Occupational Health and Environmental Health, School of Public Health at Guangxi Medical University, Nanning, Guangxi, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: qinxue919@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. Electronic address: lis8858@126.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D007376:Interleukin-2 / Q000097:blood* / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D007376:Interleukin-2
keywords: Chronic hepatitis B; Hepatocellular carcinoma; Interleukin-2; Liver cirrhosis; Polymorphism