title: FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma.
abstract: The precise mechanism of rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2-mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via immunoglobulin G (IgG) fragment C receptors (FcRs), was also proposed as a mechanism of rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85). The FCGR3A valine (V) allele was significantly correlated with a higher complete response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs 79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A polymorphisms. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of the FCGR3A gene polymorphism on response rate was not noted in the CHOP group. In terms of overall or event-free survival, no difference was found according to FCGR3A or FCGR2A alleles. The FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP, but does not correlate with survival in patients with DLBCL.
authors.affiliation: Department of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Ilwon-dong 50, Kangnam-gu, Seoul, Korea 135-710. drkiim@medimail.co.kr
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Hee Du
authors.initials: HD
authors.lastname: Jung
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Do
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Myung Soo
authors.initials: MS
authors.lastname: Hyun
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001483:Base Sequence; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004273:DNA, Neoplasm / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011241:Prednisone / Q000008:administration & dosage; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D004273:DNA, Neoplasm; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone