Tumor Biology

, Volume 37, Issue 5, pp 6343–6348 | Cite as

Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population

  • Aihua Tan
  • Yong Gao
  • Ziting Yao
  • Shining Su
  • Yonghua Jiang
  • Yuanliang Xie
  • Xiaoying Xian
  • Zengnan Mo
Original Article


IL12 plays a major role not only in inducing appropriate immune responses against viral infections (including HBV) but also in the antitumor immune response. This study was conducted to investigate the relationships of genetic variants in IL12 with hepatitis B virus (HBV) clearance and development of HBV-related hepatocellular carcinoma (HCC). We genotyped three single nucleotide polymorphisms (SNPs) of the IL12A (rs568406 and rs2243115) and IL12B (rs3212227) in 395 HBV-positive HCC patients, 293 persistent HBV carriers and 686 subjects with HBV natural clearance from southern China, using the improved multiplex ligase detection reaction (iMLDR) method. Logistic regression analysis adjusted for age, smoking, and alcohol consumption status showed that rs568408 variant genotypes were significantly associated with host HBV-related HCC risk when compared with persistent HBV carriers, and carriers of the GA + AA genotype decreased the HCC risk in comparison with GG carriers (adjusted OR = 0.53, 95 % CI 0.35–0.80, P = 0.002). No relationships between the rs2243115 and rs3212227 SNPs and HCC risk were observed (all P > 0.05). Besides, rs568408 showed an approaching significant effect on susceptibility to HBV persistent infection (adjusted OR = 1.34, 95 % CI 0.99–1.81, P = 0.057 in dominant genetic models). Furthermore, the TG haplotype was observed to be associated with a significantly increased risk of HBV-related HCC (OR = 1.42, 95 % CI 1.10–1.83, P = 0.006), while TA haplotype was associated with a decreased risk of HBV-related HCC (OR = 0.61, 95 % CI 0.45–0.83, P = 0.002). Our results reveal that the IL12A rs568408 variant may be a marker SNP for risk of both HBV clearance and HBV-related HCC development.


IL12 gene Persistent HBV infection HBV-related HCC 



This study was supported by the Guangxi Natural Science Foundation (2012GXNSFBA053117), Guangxi Natural Science Fund for Innovation Research Team (2013GXNSFFA019002), Guangxi Collaborative Innovation Center for genomic and personalized medicine (201319), Guangxi Natural Science Fund for Distinguished Young Scholars (2012jjFA40011), and Program for New Century Excellent Talents in University (NCET-12-0653).

Compliance with ethical standards

Conflicts of interest


Supplementary material

13277_2015_4520_MOESM1_ESM.doc (30 kb)
Supplementary Table 1 SNPs and PCR primer for IL12 allele genotyping. (DOC 30 kb)
13277_2015_4520_MOESM2_ESM.docx (13 kb)
Supplementary Table 2 Linkage disequilibrium (LD) information of IL12A variations (DOCX 13 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Aihua Tan
    • 1
    • 2
  • Yong Gao
    • 2
  • Ziting Yao
    • 2
  • Shining Su
    • 3
  • Yonghua Jiang
    • 2
  • Yuanliang Xie
    • 2
  • Xiaoying Xian
    • 2
  • Zengnan Mo
    • 2
  1. 1.Department of chemotherapyThe Affiliated Tumor Hospital of Guangxi Medical UniversityNanningChina
  2. 2.Center for Genomic and Personalized MedicineGuangxi Medical UniversityNanningChina
  3. 3.TalentCloud Information Technology LtdNanningChina

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