Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer
- Department of Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of)
- Department of Medical Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
- Department of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
- Department of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)
- 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, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 81; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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ANTIMETABOLITES
AZINES
BODY
DIGESTIVE SYSTEM
DISEASES
DRUGS
FLUOROURACILS
GASTROINTESTINAL TRACT
GENES
GENOTYPE
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTESTINES
LARGE INTESTINE
MEDICINE
NEOPLASMS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RECTUM
THERAPY
URACILS