The single nucleo tide polymorphism rs1800795 kinase inhibitor Baricitinib corresponding to 174G/C SNP in the IL 6 gene promoter showed higher transcriptional activity in gene reporter assays. In vivo, higher IL 6 levels were determined in carriers of the common allele in studies including both healthy subjects and patients with inflammatory diseases. A common non synonymous variant in IL 6R causes an Asp358Ala amino acid substitution within the extracellular cleavage domain of the IL 6R causing proteolytic cleavage of the membrane bound IL 6R. In in vivo studies, 358Ala carriers showed higher concentrations of the so called soluble IL 6 receptor, which is responsible of trans signaling. In several reports, an up regulated IL 6/IL6R system has shown a prognostic impact in patients with hematologic malignancies and with solid tumors.

This background and the availability of novel IL 6 targeting moAbs prompted us to investigate the possible influence of rs1800795 and rs8192284 on survival of patients with advanced gastric cancer. This information, beyond ad dressing a novel prognostic factor, may be relevant for the planning of clinical trials with anti IL 6 therapies in this lethal disease. Methods The study population consisted of consecutive patients with locally advanced, relapsed of metastatic gastric cancer who were treated with palliative chemotherapy at three participating Institution in Central Italy. One hundred seventy five patients were homogeneously treated with both first line and second line palliative chemotherapy be tween 1998 and 2006.

In 161 of 175 patients germline DNA was available from stored blood samples or obtained after DNA extraction from normal mucosa from archival paraffin embedded tissues. Data on chemother apy, treatment outcomes, baseline characteristics with routine blood chemistries, and follow up were fully avail able for the 161 assessed patients. The study approval by the main hospital research and ethics committee was granted by those of affiliate Institutions. Patients gave their general consent for the storage of their tissues and subsenquent use for research purposes. Genetic analyses Patients characteristics and their outcomes were unknown to investigators performing genetic analyses. Genomic DNA extraction using the QiaAmp kit. A polymerase chain reaction restriction fragment length polymorphism technique was used for determining the IL 6R rs8192284 A/C and the IL 6 rs1800795 G/C genotypes.

Genome DNA was used as a template and PCR was carried out using the Diatheva 2��PCR Master Mix with the following conditions 95 C 10 min . 95 C 15 sec, 60 C 30 sec, 72 C 30 sec. The two PCR were performed using the following primer Dacomitinib sets rs1800795, forward pairs were designed using the PRIMER3 program. Statistical plan The primary endpoint of the study was the association between genotypes and overall survival, as calcu lated from the start of first line palliative chemotherapy until death.