Use of germline polymorphisms in predicting concurrent chemoradiotherapy response in esophageal cancer

To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at...

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Veröffentlicht in:International journal of radiation oncology, biology, physics Jg. 82; H. 5; S. 1996
Hauptverfasser: Chen, Pei-Chun, Chen, Yen-Ching, Lai, Liang-Chuan, Tsai, Mong-Hsun, Chen, Shin-Kuang, Yang, Pei-Wen, Lee, Yung-Chie, Hsiao, Chuhsing K, Lee, Jang-Ming, Chuang, Eric Y
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.04.2012
Schlagworte:
Aged
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Chemoradiotherapy - methods
Chromosomes, Human, Pair 2 - genetics
Cisplatin - administration & dosage
Disease Progression
Esophageal Neoplasms - genetics
Esophageal Neoplasms - therapy
Esophagectomy
Fluorouracil - administration & dosage
Genome-Wide Association Study - methods
Humans
Linkage Disequilibrium - genetics
Male
Middle Aged
Models, Genetic
Polymorphism, Single Nucleotide
Prospective Studies
Radiotherapy Dosage
Remission Induction - methods
Taiwan
Treatment Outcome
Taiwan
ISSN:1879-355X, 1879-355X
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Zusammenfassung:To identify germline polymorphisms to predict concurrent chemoradiation therapy (CCRT) response in esophageal cancer patients. A total of 139 esophageal cancer patients treated with CCRT (cisplatin-based chemotherapy combined with 40 Gy of irradiation) and subsequent esophagectomy were recruited at the National Taiwan University Hospital between 1997 and 2008. After excluding confounding factors (i.e., females and patients aged ≥70 years), 116 patients were enrolled to identify single nucleotide polymorphisms (SNPs) associated with specific CCRT responses. Genotyping arrays and mass spectrometry were used sequentially to determine germline polymorphisms from blood samples. These polymorphisms remain stable throughout disease progression, unlike somatic mutations from tumor tissues. Two-stage design and additive genetic models were adopted in this study. From the 26 SNPs identified in the first stage, 2 SNPs were found to be significantly associated with CCRT response in the second stage. Single nucleotide polymorphism rs16863886, located between SGPP2 and FARSB on chromosome 2q36.1, was significantly associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.62-10.30) under additive models. Single nucleotide polymorphism rs4954256, located in ZRANB3 on chromosome 2q21.3, was associated with a 3.93-fold increase in pathologic complete response to CCRT (95% confidence interval 1.57-10.87). The predictive accuracy for CCRT response was 71.59% with these two SNPs combined. This is the first study to identify germline polymorphisms with a high accuracy for predicting CCRT response in the treatment of esophageal cancer.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:1879-355X
1879-355X
DOI:10.1016/j.ijrobp.2011.02.036