Polymorphisms of microRNA Target Genes IL12B, INSR, CCND1 and IL10 in Gastric Cancer

World J Gastroenterol. 2017 May 21;23(19):3480-3487. doi: 10.3748/wjg.v23.i19.3480.

Abstract

Aim: To evaluate associations between miRNA target genes IL12B, INSR, CCND1 and IL10 polymorphisms and gastric cancer (GC) in European population.

Methods: Gene polymorphisms were analyzed in 508 controls and 474 GC patients from 3 tertiary centers in Germany, Lithuania and Latvia. Controls were patients from the out-patient departments, who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy. Gastric cancer (GC) patients had histopathological verification of gastric adenocarcinoma. Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells. IL12B T>G (rs1368439), INSR T>C (rs1051690), CCND1 A>C (rs7177) and IL10 T>C (rs3024498) SNPs were genotyped by the real-time polymerase chain reaction. Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex, age and country of birth.

Results: We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690. The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls (23.26% and 19.19% respectively, P = 0.028). CT genotype was also more prevalent in patients compared to control group (38.48% and 30.12% respectively, P < 0.021). Logistic regression analysis revealed that only one polymorphism (rs1051690 in INSR gene) was associated with increased risk of GC. Carriers of CT genotype had higher odds of GC when compared to CC genotype (OR = 1.45, 95%PI: 1.08-1.95, P = 0.01). Similar association was observed in a dominant model for INSR gene, where comparison of TT+CT vs CC genotypes showed an increased risk of GC (OR = 1.44, 95%PI: 1.08-1.90, P = 0.01). Other analyzed SNPs were not associated with the presence of GC.

Conclusion: INSR rs1051690 SNP is associated with increased risk of GC, while polymorphisms in IL12B, CCND1 and IL10 genes are not linked with the presence of GC.

Keywords: Gastric cancer; Single-nucleotide polymorphisms; Target genes; miRNA.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Case-Control Studies
  • Cyclin D1 / genetics*
  • Female
  • Genotype
  • Germany
  • Humans
  • Interleukin-10 / genetics*
  • Interleukin-12 Subunit p40 / genetics*
  • Latvia
  • Leukocytes, Mononuclear
  • Lithuania
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptor, Insulin / genetics*
  • Regression Analysis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism

Substances

  • Antigens, CD
  • CCND1 protein, human
  • IL10 protein, human
  • IL12B protein, human
  • Interleukin-12 Subunit p40
  • Interleukin-10
  • Cyclin D1
  • INSR protein, human
  • Receptor, Insulin