Impacts of CCL4 gene polymorphisms on hepatocellular carcinoma susceptibility and development

Int J Med Sci. 2017 Jul 19;14(9):880-884. doi: 10.7150/ijms.19620. eCollection 2017.

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer globally and the third most common cause of cancer mortality. In Taiwan, HCC is the second leading cause of cancer death. CCL4 (C-C chemokine ligand 4), is a macrophage inflammatory protein with a chief effect in inflammation and immune-regulation, and was documented in cancer progression by promoting instability in the tumor environment. Polymorphisms in chemokine genes help to determine host-pathogen interactions that influence chemokine levels. We investigated the effects of CCL4 gene polymorphisms on the risk of hepatocellular carcinoma (HCC) disease progression in a cohort of Taiwanese patients. We recruited total of 1,546 participants in current study, including 1,200 healthy control and 346 patients with HCC. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were examined by a real-time PCR. We found that the A/G homozygotes of CCL4 rs10491121 polymorphism reduced the risks for HCC. On the other hand, AG and GA haplotypes of 2 CCL4 SNPs (rs1049112 and rs171915) also reduced the risks for HCC by 0.025 and 0.515 fold, respectively. The present report is the first time to examine the risk factors associated with CCL4 SNPs in HCC progression in Taiwan.

Keywords: CCL4; HCC; SNP; Susceptibility.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Chemokine CCL4 / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Taiwan

Substances

  • CCL4 protein, human
  • Chemokine CCL4