title: A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients.
abstract: Genetic factors are known to affect the efficiency of therapy with monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) in patients with metastatic colorectal cancer (mCRC). At present, the only accepted molecular marker predictive of the response to anti-EGFR mAbs is the somatic mutation of KRAS and NRAS as a marker of resistance to anti-EGFR. However, only a fraction of KRAS wild-type patients benefit from that treatment. In this study, we show that the EGFR gene polymorphism rs1050171 defines, independently of RAS mutational status, a sub-population of 11 % of patients with a better clinical outcome after anti-EGFR treatment. Median PFS for patients with the GG genotype was 10.17 months compared to 5.37 of those with AG + AA genotypes. Taken together, our findings could be used to better define CRC populations responding to anti-EGFR therapy. Further studies in larger independent cohorts are necessary to validate the present observation that a synonymous polymorphism in EGFR gene impacts on clinical responsiveness.
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Hospital-Surgical Pathology Building, Strada di Fiume 447, 34149, Trieste, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bonin
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Hospital-Surgical Pathology Building, Strada di Fiume 447, 34149, Trieste, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Donada
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bussolati
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Hospital-Surgical Pathology Building, Strada di Fiume 447, 34149, Trieste, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Nardon
authors.affiliation: Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: Division of Oncology-Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Unit of Anatomical Pathology, Ospedale di Circolo, Varese, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Chiaravalli
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, Varese, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Capella
authors.affiliation: Institute of Pathology-Medical University of Graz, Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.affiliation: Department of Medical Sciences, University of Trieste, Cattinara Hospital-Surgical Pathology Building, Strada di Fiume 447, 34149, Trieste, Italy. stanta@icgeb.org.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stanta
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary*; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage / Q000627:therapeutic use*; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D018773:Genes, erbB-1; D011905:Genes, ras; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077544:Panitumumab; D020641:Polymorphism, Single Nucleotide; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D003062:Codon; C117307:KRAS protein, human; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D000077544:Panitumumab; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: EGFR gene polymorphism rs1050171; FFPE; RAS mutation; Survival; Synonymous SNP; mCRC