Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer

Journal Article · Tue Nov 01 00:00:00 EDT 2011 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2010.06.049· OSTI ID:21590424

Hur, Hyuk; Kang, Jeonghyun ^[1]; Min, Byung Soh; Lee, Kang Young ^[1]; Shin, Sang Joon ^[2]; Keum, Ki Chang ^[3]; Choi, Junjeong; Kim, Hoguen ^[4]; Choi, Sung Ho; Lee, Mi-Young ^[5]

---

1. Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of)
2. Department of Medical Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
3. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
4. Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
5. ISU ABXIS Co., Ltd., Seoul (Korea, Republic of)

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.

• OSTI ID: 21590424
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 81, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2010.06.049; PII: S0360-3016(10)00903-X; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
FLUOROURACILS
GENES
GENOTYPE
NEOPLASMS
NUCLEOTIDES
RECTUM
THERAPY
ANTIMETABOLITES
AZINES
BODY
DIGESTIVE SYSTEM
DISEASES
DRUGS
GASTROINTESTINAL TRACT
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTESTINES
LARGE INTESTINE
MEDICINE
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
URACILS