Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6

Title
Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6
Author(s)
이경희한새원[한새원]오도연[오도연]임석아[임석아]박숙련[박숙련]이근욱[이근욱]송홍석[송홍석]이남수[이남수]최인실[최인실]이문희[이문희]김민아[김민아]김우호[김우호]Yung-Jue Bang[Yung-Jue Bang]김태유[김태유]
Keywords
METASTATIC COLORECTAL-CANCER; CELL LUNG-CANCER; PHASE-III TRIAL; EGFR GENE; CHEMOTHERAPY; MUTATIONS; EXPRESSION; GEFITINIB; PREDICTS; SEQUENCE
Issue Date
201005
Publisher
WILEY-BLACKWELL
Citation
CANCER SCIENCE, v.101, no.3, pp.793 - 799
Abstract
Cetuximab is a monoclonal antibody targeting epidermal growth factor receptor (EGFR). The present study investigated the association between germline genetic polymorphisms and the treatment outcome of cetuximab plus modified leucovovin, fluorouracil, and oxaliplatin (FOLFOX) 6 chemotherapy in advanced gastric cancer (AGC). DNA from peripheral blood mononuclear cells of 38 patients enrolled in a phase II study of cetuximab plus modified FOLFOX6 were analyzed for 16 polymorphisms in eight genes (EGFR, epidermal growth factor, transforming growth factor-alpha (TGFA), thymidylate synthase, excision repair cross-complementation group 1, Xeroderma pigmentosum group D, and fragment c gamma receptors (FCGR)2A and 3A). The EGFR intron 1 CA repeat polymorphism was associated with survival. Twenty-one patients had low repeats (sum of both alleles <= 37), and 17 patients had high repeats (sum >= 38). Patients with low CA repeats had longer progression-free survival (adjusted hazard ratio [HR] 0.42 [95% confidence interval [CI] 0.19-0.96], P = 0.040) and overall survival (adjusted HR 0.40 [95% CI 0.16-0.99], P = 0.048) compared with patients with high CA repeats. In addition, the tumor EGFR expression was higher in patients with a lower number of CA repeats. The association between the CA repeat status and survival was not found in a separate cohort of AGC patients (n = 68) treated only with modified FOLFOX6. These results suggest that the EGFR intron 1 CA repeat polymorphism could be a useful, predictive biomarker of cetuximab efficacy in AGC and merits further investigation in randomized studies. (Cancer Sci 2010; 101: 793-799)
URI
http://hdl.handle.net/YU.REPOSITORY/22436http://dx.doi.org/10.1111/j.1349-7006.2009.01447.x
ISSN
1347-9032
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의과대학 > 내과학교실 > Articles
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