Evaluation of the circulating levels of IL-۱۲ and IL-۳۳ in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms

Objective(s):IL-۱۲ as an anti-tumor cytokine and IL-۳۳ 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-۱۲ and IL-۳۳ levels and single nucleotide polymorphisms (SNP) in their genes in patients with breast cancer. Materials and Methods:Blood samples were collected from ۱۰۰ patients with breast cancer, and ۱۰۰ healthy women were controls. The serum IL-۱۲ and IL-۳۳ levels were measured by ELISA. The SNP rs۳۲۱۲۲۲۷ (in IL-۱۲ gene) and rs۱۹۲۹۹۹۲ (in IL-۳۳ gene) were determined using PCR-RFLP. Results:The IL-۱۲ levels similarly expressed in patients and controls. IL-۱۲ levels in patients at stage I were significantly lower than in the healthy group (P<۰.۰۵). IL-۳۳ levels and the IL-۳۳/IL-۱۲ ratio were significantly higher in patients than the control group (P<۰.۰۰۱). The IL-۳۳ levels and IL-۳۳/IL-۱۲ ratio in stage IV patients were significantly higher than other stages and controls (PP<۰.۰۰۱, respectively). There were no significant differences in the frequencies of genotypes in rs۳۲۱۲۲۲۷ and rs۱۹۲۹۹۹۲ between patients and the control group. No significant differences were observed between subjects with various genotypes at rs۳۲۱۲۲۲۷ and rs۱۹۲۹۹۹۲ with respect to related cytokine levels. Conclusion:These results indicate that the diminished IL-۱۲ production may contribute to the tumor establishment. The higher IL-۳۳ levels and IL-۳۳/IL-۱۲ ratio in patients also indicate an imbalance in Th۱/Th۲ responses that may contribute to tumor development. Thus, correcting the imbalance of Th۱/Th۲ could be an important strategy for cancer immunotherapy.

کلیدواژه ها:

Breast Cancer ، Interleukin-۱۲ ، Interleukin-۳۳ ، Single nucleotide -polymorphism ، Tumor stages