title: Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms.
abstract: OBJECTIVE
  IL-12 as an anti-tumor cytokine and IL-33 a novel identified cytokine with both pro- or anti-tumor activities, play important roles in response against tumor cells. Our aim was to evaluate the IL-12 and IL-33 levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer.
  
  
  METHODS
  Blood samples were collected from 100 patients with breast cancer, and 100 healthy women were controls. The serum IL-12 and IL-33 levels were measured by ELISA. The SNP rs3212227 (in IL-12 gene) and rs1929992 (in IL-33 gene) were determined using PCR-RFLP.
  
  
  RESULTS
  The IL-12 levels similarly expressed in patients and controls. IL-12 levels in patients at stage I were significantly lower than in the healthy group (P<0.05). IL-33 levels and the IL-33/IL-12 ratio were significantly higher in patients than the control group (P<0.001). The IL-33 levels and IL-33/IL-12 ratio in stage IV patients were significantly higher than other stages and controls (P<0.0001 and P<0.001, respectively). There were no significant differences in the frequencies of genotypes in rs3212227 and rs1929992 between patients and the control group. No significant differences were observed between subjects with various genotypes at rs3212227 and rs1929992 with respect to related cytokine levels.
  
  
  CONCLUSIONS
  These results indicate that the diminished IL-12 production may contribute to the tumor establishment. The higher IL-33 levels and IL-33/IL-12 ratio in patients also indicate an imbalance in Th1/Th2 responses that may contribute to tumor development. Thus, correcting the imbalance of Th1/Th2 could be an important strategy for cancer immunotherapy.
authors.affiliation: Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Abdollah
authors.initials: A
authors.lastname: Jafarzadeh
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran; Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Kayhan
authors.initials: K
authors.lastname: Minaee
authors.affiliation: Department of Laboratory Sciences, Paramedical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ali-Reza
authors.initials: AR
authors.lastname: Farsinejad
authors.affiliation: Department of Laboratory Sciences, Paramedical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nemati
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Arezu
authors.initials: A
authors.lastname: Khosravimashizi
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Daneshvar
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mohammad Mehdi
authors.initials: MM
authors.lastname: Mohammadi
authors.affiliation: Department of Immunology, Medical School, Dezful University of Medical Sciences, Dezful, Iran.
authors.forename: Abdolkarim
authors.initials: A
authors.lastname: Sheikhi
authors.affiliation: Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghaderi
keywords: Breast cancer; Interleukin-12; Interleukin-33; Single nucleotide -polymorphism; Tumor stages