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Thymidylate synthase gene polymorphism affects the response to preoperative 5-fluorouracil chemoradiation therapy in patients with rectal cancer

Authors
 이강영 ; 허혁 ; 강정현 ; 금기창 ; 김남규 ; 김호근 ; 민병소 ; 신상준 
Citation
 International Journal of Radiation Oncology Biology Physics, Vol.81(3) : 669~676, 2011 
Journal Title
 International Journal of Radiation Oncology Biology Physics 
ISSN
 0360-3016 
Issue Date
2011
Abstract
PURPOSE: This study aims to correlate thymidylate synthase (TS) gene polymorphisms with the tumor response to preoperative 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) in patients with rectal cancer. METHODS AND MATERIALS: Forty-four patients with rectal cancer treated with 5-FU-based preoperative CRT were prospectively enrolled in this study. Thymidylate synthase expression and TS gene polymorphisms were evaluated in tumor obtained before preoperative CRT and were correlated with the pathologic response, as assessed by histopathologic staging (pTNM) and tumor regression grade. RESULTS: Patients exhibited 2R/3R and 3R/3R tandem repeat polymorphisms in the TS gene. With regard to TS expression in these genotypes, 2R/3RC and 3RC/3RC were defined as the low-expression group and 2R/3RG, 3RC/3RG, and 3RG/3RG as the high-expression group. There was no significant correlation between TS expression and tumor response. There was no significant difference in the tumor response between patients homozygous for 3R/3R and patients heterozygous for 2R/3R. However, 13 of 14 patients in the low-expression group with a G>C single-nucleotide polymorphism (SNP) (2R/3RC [n = 5] or 3RC/3RC [n = 9]) exhibited a significantly greater tumor downstaging rate, as compared with only 12 of 30 patients in the high-expression group without the SNP (2R/3RG [n = 10], 3RC/3RG [n = 9], or 3RG/3RG [n = 11]) (p = 0.001). The nodal downstaging rate was also significantly greater in this low-expression group, as compared with the high-expression group (12 of 14 vs. 14 of 30, p = 0.014). However, there was no significant difference in the tumor regression grade between these groups. CONCLUSIONS: This study suggests that SNPs within the TS enhancer region affect the tumor response to preoperative 5-FU-based CRT in rectal cancer.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/94405
DOI
10.1016/j.ijrobp.2010.06.049
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Radiation Oncology
1. 연구논문 > 1. College of Medicine > Dept. of Surgery
1. 연구논문 > 1. College of Medicine > Dept. of Pathology
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S036030161000903X
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