FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Abstract Text:

Wu Zhang,Michael Gordon,Anne M Schultheis,Dong Yun Yang,Fumio Nagashima,Mizutomo Azuma,Heung-Moon Chang,Eva Borucka,Georg Lurje,Andy E Sherrod,Syma Iqbal,Susan Groshen,Heinz-Josef Lenz,

PURPOSE: Cetuximab, a chimeric immunoglobulin G 1 (IgG1) anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), has shown efficacy in 10% of patients with metastatic colorectal cancer (CRC). Recent studies demonstrate antibody-dependent cell-mediated cytotoxicity (ADCC) is one of the modes of action for rituximab and trastuzumab. Fragment c (Fc) portion of IgG1 mAb has shown to induce ADCC. Fragment c gamma receptors (FcgammaR) play an important role in initiating ADCC. Studies have shown that two IgG FcgammaR polymorphisms (FCGR2A-H131R and FCGR3A-V158F) independently predict response to rituximab in patients with follicular lymphoma. We tested the hypothesis of whether these two polymorphisms are associated with clinical outcome in metastatic CRC patients treated with single-agent cetuximab. PATIENTS AND METHODS: Thirty-nine metastatic CRC patients were enrolled onto the ImClone0144 trial. Using an allele-specific polymerase chain reaction (PCR) -based method, gene polymorphisms of FCGA2A-H131R and FCGA3A-V158F were assessed from genomic DNA extracted from peripheral blood samples. RESULTS: FCGR2A-H131R and FCGR3A-V158F polymorphisms were independently associated with progression-free survival (PFS; P = .037 and .055, respectively; log-rank test). Combined analysis of these two polymorphisms showed that patients with the favorable genotypes (FCGR2A, any histidine allele, and FCGR3A, any phenylalanine allele) showed a median PFS of 3.7 months (95% CI, 2.4 to 4.4 months), whereas patients with any two unfavorable genotypes (FCGR2A arginine/arginine or valine/valine) had a PFS of 1.1 months (95% CI, 1.0 to 1.4 months; P = .004; log-rank test). CONCLUSION: Our preliminary data suggest that these two polymorphisms may be useful molecular markers to predict clinical outcome in metastatic CRC patients treated with cetuximab and that they may indicate a role of ADCC of cetuximab.

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Publishing Authors By Initials

W Zhang,M Gordon,AM Schultheis,DY Yang,F Nagashima,M Azuma,HM Chang,E Borucka,G Lurje,AE Sherrod,S Iqbal,S Groshen,HJ Lenz,

For similar investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research abstracts see: investigative techniques: epidemiologic methods: data collection: vital statistics: mortality: survival rate research

PUBMED ID PMID:

MEDLINE DATE:

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of clinical oncology : official journal of

VOLUME: 25

Page Numbers: 3712-8

Journal Abbreviation: J. Clin. Oncol.

ISSN: 1527-7755

DAY: 20

MONTH: Aug

YEAR: 2007

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8309333

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Keywords Mesh Terms:

KEYWORDS: Survival Rate

MESH TERMS: genetics

Chemical & Substance for Abstract: FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab. Information

Substance Name: Receptor, Epidermal Growth Factor

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.

AFFILIATION: Division of Medical Oncology, Department of Pathology, University of Southern California, Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.

Country: United States

AGENCY: United States NCI

GRANT: 5 P30CA14089-271

ACRONYM: CA

MEDLINETA: J Clin Oncol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab Related Publications

• An elective course on lifestyle modifications in pharmacotherapy.
• Analysis of synchrony demonstrates that the presence of "pain networks" prior to a noxious stimulus can enable the perception of pain in response to that stimulus.
• Association of methylenetetrahydrofolate reductase gene polymorphisms and sex-specific survival in patients with metastatic colon cancer.
• Capecitabine: the new generation of fluoropyrimidines in colorectal cancer.
• EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.
• Endogenous and exogenous modulators of potentials evoked by a painful cutaneous laser (LEPs).
• Estimation of illumination characteristics.
• Expression of the p60 autolysin enhances NK cell activation and is required for listeria monocytogenes expansion in IFN-gamma-responsive mice.
• FCGR2A and FCGR3A polymorphisms associated with clinical outcome of epidermal growth factor receptor expressing metastatic colorectal cancer patients treated with single-agent cetuximab.
• Fat elimination in acute renal failure.
• Gene expression levels of epidermal growth factor receptor, survivin, and vascular endothelial growth factor as molecular markers of lymph node involvement in patients with locally advanced rectal cancer.
• Imaging central pain syndromes.
• Internal pallidal neuronal activity during mild drug-related dyskinesias in Parkinson's disease: decreased firing rates and altered firing patterns.
• Lung perforation by nasogastric feeding tubes.
• Management and preparedness for infusion and hypersensitivity reactions.
• Mechanoreceptors in calanoid copepods: designed for high sensitivity.
• Molecular prognostic markers in locally advanced colon cancer.
• Optical polar profilometer: an analyzer of circularly symmetric surfaces.
• Role of inflammation in diabetic nephropathy.
• Spontaneous low threshold spike bursting in awake humans is different in different lateral thalamic nuclei.
• Thymidylate synthase haplotype is associated with tumor recurrence in stage II and stage III colon cancer.
• Two stage principal component analysis of color.
• [Central nervous system regulation of gastric acid and duodenal bicarbonate secretion]
• [Clinical experiences with treatment of granulosa cell tumors]
• [Hormone substitution after carcinoma]
• [Not Available.]
• [Not Available.]
• [Not Available.]
• [Steatohepatitis and cirrhosis: first manifestation 23 years after jejunoileal bypass surgery.]
• [The status of intraperitoneal chemotherapy]