title: How gene polymorphisms can influence clinical response and toxicity following R-CHOP therapy in patients with diffuse large B cell lymphoma.
abstract: The treatment of diffuse large B cell lymphoma (DLBCL) is generally based on multidrug chemotherapy, for instance the therapy with rituximab together with cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). A significant proportion of DLBCL patients benefit from rituximab-based chemoimmunotherapy. However, among patients with DLBCL toxic effects due to therapy treatment are still very frequent, as well as inter-individual differences in the outcomes of patients even having similar stage, histological grade and histopathological type of the tumor. The present paper reviews the actual status of pharmacogenomics studies concerning gene polymorphisms that may affect response and tolerability to R-CHOP therapeutic regimen used to treat DLBCL. There are clear evidences that polymorphisms of genes codifying for protein are involved in cytotoxicity induced by R-CHOP regimen. Moreover, polymorphisms in genes encoding TNF-superfamily cytokines and proteins involved in controlling cellular cycle and tumor growth may be related to variability in efficacy of R-CHOP therapy in DLBCL patients. This knowledge emphasizes the clinical meaning and importance of pharmacogenetics in oncology. The main merit of our study seems to have tried for the first time a comprehensive review of gene polymorphisms that are involved in the response to an entire therapeutic protocol, R-CHOP, in a specific disease, DLBCL, rather than examining polymorphisms referred to individual drugs among themselves not connected or used to treat different pathological conditions. Indeed, it seems clear that only the analysis of a constellation of polymorphisms can really be useful in clinical practice, while knowledge of a single polymorphism seems to give a limited contribution to our ability to use genetic analysis to the management of patients with malignant blood disorders.
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: angelaf91@hotmail.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Falduto
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: fcimino@unime.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cimino
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: specialea@unime.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Speciale
authors.affiliation: Division of Hematology, Department of General Surgery and Oncology, University of Messina, Messina, Italy. Electronic address: cmusolino@unime.it.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.affiliation: School and Division of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University Hospital "G. Martino", Messina, Italy; Institute of Clinical Physiology, IFC CNR, Messina Unit, Messina, Italy. Electronic address: gangemis@unime.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Gangemi
authors.affiliation: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy. Electronic address: asaija@unime.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Saija
authors.affiliation: Division of Hematology, Department of General Surgery and Oncology, University of Messina, Messina, Italy. Electronic address: aallegra@unime.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Allegra
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D000071185:Pharmacogenomic Testing; D011110:Polymorphism, Genetic / Q000187:drug effects; D011241:Prednisone / Q000009:adverse effects / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects; D014750:Vincristine / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; C571759:R-CHOP protocol; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Diffuse large B cell lymphoma; Drug toxicity; Gene polymorphisms; Pharmacogenetics; Prognostic stratification methods; R-CHOP regimen