Correlation Between Interleukin IL-6/IL-6 Receptor Polymorphisms (IL6–174C>G and IL6R 1073A>C) and RAS/BRAF Mutations in Patients with Colorectal Cancer

Background: Chronic inflammation is an important factor in the development and progression of colorectal cancer (CRC). One of the key participants of chronic inflammation is interleukin-6 (IL-6), which enhances tumor malignancy. Some of the genetic markers characterizing the IL-6/STAT3/JAK pathway are functional polymorphisms in IL6 and IL6R genes. Hyperexpression of IL-6 and increasing concentrations of the soluble form, IL-6R, may be one possible option for cross-activation of MAPK signaling. Methods: Detection of rs1800795 and rs2228145 SNPs was carried out using allele-specific PCR. The mutations of RAS and BRAF genes in tumors were determined by pyrosequencing. Results: The allele and genotype distributions of IL6 rs1800795 (−174C>G) and IL6R rs2228145 (1073A>C) were significantly different between the CRC and control groups. Thus, the risks of CRC developing in carriers of the homozygous G/G rs1800795 and C/C rs2228145 genotypes were 2.05- and 1.85-fold higher. Also, we identified a relationship between the studied SNPs and somatic activating mutations in the RAS and BRAF genes. It was found that the G/G rs1800795 and C/C rs2228145 genotypes are significantly more common in the group of patients without activating mutations in the RAS and BRAF genes. Conclusions: Understanding the impact of genetic factors not only on cancer predisposition but the evolution of cancer cells will help to derive novel predictive markers and therapy options.