IL-6 polymorphism in non-small cell lung cancer: a prognostic value?

Mónica Gomes, Ana Coelho, António Araújo, Andreia Azevedo, Ana Luísa Teixeira, Raquel Catarino, Rui Medeiros

Lung cancer was found to be the most commonly diagnosed cancer, as well as the primary cause of cancer-related mortality for males worldwide and the second leading cause of cancer-related deaths for women. Cytokines are fundamental for several biological processes-associated malignant tumors. The IL-6 is a cytokine involved in the regulation of cellular functions including processes associated with cancer, such as proliferation, apoptosis, angiogenesis, and differentiation. Furthermore, IL-6 is a potent pleiotropic inflammatory cytokine that is considered a key growth-promoting and antiapoptotic factor. The polymorphism - 174G/C SNP is a G to C transition in the -174 position of the promoter region of the IL-6 gene. The aim of our study was to evaluate the influence of -174G/C polymorphism in clinical outcome of non-small cell cancer (NSCLC) patients. DNA was extracted from peripheral blood of 424 patients diagnosed with cytologically or histologically NSCLC. The characterization of IL-6 -174G/C genotypes was performed by PCR-RFLP (NlaIII). IL-6 polymorphism's genotypes were divided according to functional activity, so the G carriers (CG/GG) is the high-producer IL-6, and CC genotype is the low-producer IL-6. Regarding survival, we verify that patients with genotypes carrying the G allele (CG/GG) had a statistically significant diminished survival when compared with patients with CC genotype (62.79 and 42.31 months, respectively; P = 0.032). In the promoter region of the IL-6 gene, polymorphic variants were located and may be responsible for alterations in transcription that consequently affect serum levels of the cytokine. With our study, we demonstrated that genetic variant (-174G/G and G/C) can be responsible for changes in prognosis of NSCLC patients.