FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma

Rituximab therapy in malignant lymphoma

“…The Fc receptor (FcgR) of effector cells has two alleles and the valine/valine (V/V) allele of FcgRIIIa that confers a higher affinity for IgG1 and rituximab is associated with an increase responsiveness to rituximab (Cartron et al, 2002;Weng and Levy, 2003). If the clinical relevance of the FcgRIIIa receptor dimorphism was established in a number of studies with rituximab used alone, it does not seem to play a major role when rituximab is used in combination with chemotherapy (Boettcher et al, 2004) even if one study showed an increased response for patients with the V/V allele without difference for progression-free survival (PFS) or overall survival (OS) (Kim et al, 2006).…”

Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21

“…[9][10][11][12][13][14]16,20 SNPs were selected according to the following criteria: (1) nonsynonymous SNPs predicting alteration of protein function; (2) SNPs affecting regulatory regions and predicting altered expression of the gene; (3) SNPs known to be relevant for prediction of outcome or toxicity in other settings and (4) SNPs with a minor allele frequency in the study population 45%. 21 In fact, SNPs whose minor alleles do not reach a given frequency in the study population may not be informative for correlation studies.…”

“…[3][4][5] According to available evidence, genes that a priori may be involved in R-CHOP pharmacogenetics encode: (1) cytochrome P450 enzymes, which promote both cyclophosphamide conversion to active compounds and metabolism of vincristine and prednisone; 11 (2) glutathione S-transferase isoforms, which promote detoxification of cyclophosphamide and vincristine and also favor scavenging of doxorubicinderived reactive oxygen species (ROS) that contribute to anthracyclin cytotoxicity; 10,15 (3) ATP-binding cassette transporters, which increase efflux of doxorubicin, vincristine and prednisone from the cell cytoplasm to the extracellular compartment; 9 (4) nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits involved in ROS generation; 14 (5) glucocorticoid receptor 16 and (6) Fcg receptors involved in rituximab antibody-dependent cellular toxicity. 12,13 This study aimed at verifying whether SNPs modulating gene expression and/or function of enzymes involved in R-CHOP pharmacogenetics may contribute to the prognostic stratification and the prediction of toxicity in DLBCL patients treated with R-CHOP21.…”

“…[8][9][10][11] Scant information is available on the impact of pharmacogenetics as a predictor of outcome and toxicity in the context of DLBCL. [12][13][14] Rituximab-CHOP (R-CHOP) is the standard treatment for DLBCL. [3][4][5] According to available evidence, genes that a priori may be involved in R-CHOP pharmacogenetics encode: (1) cytochrome P450 enzymes, which promote both cyclophosphamide conversion to active compounds and metabolism of vincristine and prednisone; 11 (2) glutathione S-transferase isoforms, which promote detoxification of cyclophosphamide and vincristine and also favor scavenging of doxorubicinderived reactive oxygen species (ROS) that contribute to anthracyclin cytotoxicity; 10,15 (3) ATP-binding cassette transporters, which increase efflux of doxorubicin, vincristine and prednisone from the cell cytoplasm to the extracellular compartment; 9 (4) nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase subunits involved in ROS generation; 14 (5) glucocorticoid receptor 16 and (6) Fcg receptors involved in rituximab antibody-dependent cellular toxicity.…”

Germline pharmacogenomics in oncology: Decoding the patient for targeting therapy

“…FcgRIIa-131H/R; FcgRIIIa-158 V/F NO 1) Some conflicting data; positive data mostly from small studies Bibeau et al, 2009;Musolino et al, 2008;Kim et al, 2006;Weng and Levy, 2003;Carlotti et al, 2007 false discovery is minimized either (optimally) by inclusion of a replication set, or by conservative adjustment for multiple comparisons (Chanock et al, 2007;van den Oord, 2008). Studies which are underpowered to adequately test less common variantsdvariants which in reality may be potentially important pharmacogenomic markersdcan have (falsely) negative results and can confuse the ability to understand conflicting data from several studies on a given drugegene pair.…”