Outcome in patients with advanced colorectal cancerLaetitia Dahan,,Emmanuelle ON 014185 cost Norguet,MarieChristine EtienneGrimaldi,JeanLouis Formento,Mohamed Gasmi,Isabelle Nanni,Jean Gaudart,St hane Garcia,L’Houcine Ouafik,JeanFran is Seitz and G ard MilanoAbstractBackground: We analyzed the influence of germinal polymorphisms of candidate genes potentially related to EGFR signalling (EGFR,EGF,CCND) or antibodydirected cell cytotoxicity (FCGRA and FCGRA) on outcome of colorectal cancer (CRC) patients getting cetuximabbased therapy. Procedures: Fiftyeight sophisticated CRC individuals treated with cetuximabirinotecan salvage therapy amongst and have been analyzed (mean age ; PS ). The following polymorphisms were analyzed on blood DNA: EGFR (CA repeats in intron , G T,C A,RK),EGF (AG),CCND (AG),FCGRA (RH),FCGRA (FV). Statistical analyses were carried out on the total population and on sufferers with wt KRas tumors. All SNPs had been regarded as as ternary variables (wtwt vs wtmut vs mutmut),together with the exception of C A EGFR polymorphism (AA patient merged with CA sufferers). Outcomes: Evaluation of skin toxicity as a function of EGFR intron polymorphism showed a tendency for higher toxicity in patients with a low quantity of CArepeats (p). CCND AG polymorphism was significantly associated with clinical response,each in the entire population and in KRas wt individuals,with the G allele becoming associated having a lack of response. In wt KRas sufferers,time to progression (TTP) was drastically related to EGFR C A polymorphism using a longer TTP in CC individuals as compared to other people,and to CCND AG polymorphism with the G allele becoming related having a shorter TTP; a multivariate evaluation like these two polymorphisms only retained CCND polymorphism. Overall survival was considerably related to CCND polymorphism having a shorter survival in patients bearing the G allele,and to FCGRA FV polymorphism using a shorter survival in VV individuals (within the entire population and in KRas wt patients). FCGRA FV and CCND AG polymorphisms had been important independent predictors of general survival. Conclusions: Present original data obtained in wt KRas patients corresponding to the current cetuximabtreated population clearly suggest that CCND AG polymorphism may perhaps be used as an additional marker for predicting cetuximab efficacy,TTP and general survival. In addition,FCGRA FV polymorphism was a significant independent predictor of overall survival. Keywords: EGFR inhibitors,cetuximab,clinical outcome,colorectal cancer,polymorphisms Correspondence: laetitia.dahanmail.aphm.fr Contributed equally Assistance PubliqueH itaux de PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/21157309 Marseille,H ital Timone,Universitde la M iterran ,Marseille,France Full list of author details is available in the finish from the article Dahan et al; licensee BioMed Central Ltd. This really is an Open Access post distributed under the terms in the Inventive Commons Attribution License (http:creativecommons.orglicensesby.),which permits unrestricted use,distribution,and reproduction in any medium,provided the original work is adequately cited.Dahan et al. BMC Cancer ,: biomedcentralPage ofIntroduction In spite of the introduction of new remedies,the year survival price for metastatic colorectal cancer (mCRC) remains under . Cetuximab,an IgG monoclonal antibody (MoAb) targeting epidermal growth issue receptor (EGFR),has confirmed to become efficient in offering clinical benefit in approximately to of patients . EGFR is actually a transmembrane tyrosine kinase receptor that,following ligand binding,triggers two m.
