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

AbstractPURPOSE:
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.
AuthorsHyuk Hur, Jeonghyun Kang, Nam Kyu Kim, Byung Soh Min, Kang Young Lee, Sang Joon Shin, Ki Chang Keum, Junjeong Choi, Hoguen Kim, Sung Ho Choi, Mi-Young Lee
JournalInternational journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 81 Issue 3 Pg. 669-76 (Nov 01 2011) ISSN: 1879-355X [Electronic] United States
PMID20932673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Antimetabolites, Antineoplastic
  • Thymidylate Synthase
  • Fluorouracil
Topics
  • Adenocarcinoma (enzymology, genetics, pathology, therapy)
  • Adult
  • Aged
  • Antimetabolites, Antineoplastic (therapeutic use)
  • Chemoradiotherapy (methods)
  • Female
  • Fluorouracil (therapeutic use)
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Genetic (genetics)
  • Polymorphism, Single Nucleotide (genetics)
  • Preoperative Care (methods)
  • Prospective Studies
  • Rectal Neoplasms (enzymology, genetics, pathology, therapy)
  • Remission Induction
  • Tandem Repeat Sequences (genetics)
  • Thymidylate Synthase (genetics, metabolism)

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