A study on the effect of IL-6 gene polymorphism on the prognosis of non-small-cell lung cancer.

Background: Lung cancer is one of the most commonly diagnosed clinical diseases. IL-6 is a multifunctional cytokine that is related to chemotactic factors and tumor biological regulation. -174G/C polymorphism in the promoter region of the IL-6 gene single-nucleotide polymorphism is the -174 position change from G to C. However, the relationship between the IL-6 gene polymorphism and prognosis of lung cancer is elusive. Therefore, the aim of this study was to evaluate the effect of -174G/C polymorphism on the prognosis of patients with non-small-cell lung cancer (NSCLC).

Methods: DNA was extracted from the peripheral blood of 434 cases diagnosed with NSCLC by cytologic or histologic examination. Polymerase chain reaction-restriction fragment length polymorphism (NlaIII) was used to detect the genotype of -174G/C. Based on the functional activity of the IL-6 gene polymorphism, genotypes were divided into G vector (CG/GG) (high yield) and CC genotype (low yield). Prognosis of patients was analyzed and independent risk factors evaluated. A quantitative analysis of the degree of pain after diagnosis was performed to evaluate the correlations between gene polymorphisms and the degree of pain and use of analgesics.

Results: Survival analysis showed that survival of the patients carrying the G allele (CG/GG) was significantly lower than that of patients with CC genotype (42.31 versus 62.79 months; P=0.032). The IL-6 gene promoter region revealed the presence of polymorphic variants, which may be associated with changes in the gene transcription process that affect the level of serum cytokines. IL-6 -174G/C gene polymorphism is associated with a significant morphine equivalent daily dose (IL-6 GG, 69.61; GC, 73.17; CC, 181.67; P=0.004). Homozygous IL-6 -174C/C genotype carriers required higher doses of opioids than GG or GC carriers.

Conclusions: Polymorphism of -174G/C in IL-6 is closely related to cancer pain in NSCLC patients, the use of analgesics, and survival prognosis. It is necessary to further confirm the related results and determine the underlying pathogenic mechanisms.