title: Genetic modulation of the interleukin 6 (IL-6) system in patients with advanced gastric cancer: a background for an alternative target therapy.
abstract: BACKGROUND
  IL-6 triggers oncogenic/angiogenic signals and the cytokine-dependent pro-cachexia cascade. The prognostic role of the functional IL-6 (promoter) rs1800795 and the IL-6R (receptor) rs8192284 single nucleotide polymorphisms (SNP) was studied in patients with advanced gastric cancer treated with palliative chemotherapy.
  
  
  METHODS
  One-hundred-sixty-one patients were genotyped for rs1800795 and rs8192284 SNPs using polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) analysis assay. These results were studied for association with overall survival (OS).
  
  
  RESULTS
  In 161 assessable patients, frequencies of rs1800795 G/G, G/C and C/C genotypes were 46%, 42% and 12%, respectively. Frequencies of rs8192284 A/A, A/C and C/C genotypes were 36%, 45% and 19%, respectively. Carriers of the rs1800795 G/G and rs8192284 C/C genotypes showed the worst OS. In the multivariate model, rs1800795 G/G (1.69 hazard ratio; 95% confidence interval 1.18-2.42), and rs8192284 C/C (1.78 hazard ratio; 95% confidence interval 1.12-2.83) confirmed an adverse prognostic impact.
  
  
  CONCLUSIONS
  In this population, genetic variants that up-regulate the IL-6 system showed impact on OS. This findings sustain the hypothesis that anti-IL-6 compounds deserve clinical studies as novel therapeutics in the palliative treatment of cancer patients.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino, Urbino, Italy. annamaria.ruzzo@uniurb.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Catalano
authors.forename: Emanuele
authors.initials: E
authors.lastname: Canestrari
authors.forename: Elisa
authors.initials: E
authors.lastname: Giacomini
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Giammaria
authors.initials: G
authors.lastname: Fiorentini
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
chemical_list: C508603:IL6R protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6