대장암의 예후 인자로서 Thymidylate Synthase 유전자 다형성의 의의
Thymidylate Synthase Gene Polymorphism as a Prognostic Factor for the Colorectal Cancer
김주형, 김영배, 최진혁, 김정미, 정수현, 서광욱,
소속 상세정보
김주형 ( Kim Joo-Hyung )
아주대학교 의과대학 외과학교실
김영배 ( Kim Young-Bae )
아주대학교 의과대학 병리학교실
최진혁 ( )
이화여자대학교 의과대학 내과학교실
김정미 ( Kim Jung-Mi )
Petagen.Inc
정수현 ( Jung Soo-Hyun )
Petagen.Inc
서광욱 ( Suh Kwang-Wook )
아주대학교 의과대학 외과학교실
KMID : 0356720040200030151
Abstract
Purpose: Thymidylate synthase (TS) expression in colorectal cancer is regarded as both a prognostic marker and a predictor of response to fluoropyrimidine-based therapies targeting TS. However, results from immunohistochemical staining of TS show wide discrepancies. The human TS gene promoter is polymorphic, having either double or triple tandem repeats of a 28-bp sequence. Here, we determined the significance of this polymorphism in predicting the clinical outcomes for patients with operable colorectal cancer treated by a curative resection.
Methods: The cases of 121 patients with stage II or III colorectal cancer, who underwent a curative resection, were reviewed. After DNA extraction from paraffin- embedded tissues, the promoter region of the TS gene was amplified by polymerase chain reaction.
Results: Sixty-eight subjects were homozygotes for the triple repeat variant (group A, L/L, 250-bp), and 53 subjects (group B) were either homozygotes for the double repeat variant (S/S, 220-bp) or heterozygotes (S/L, 220 and 250- bp). The difference between stage II and stage III patients was significant with regard to the 5-year actuarial survival (87% vs 63%, P=0.0320). Examining the survival according to the TS polymorphism, we found a significant difference between group A and B (80% vs 53%, P=0.0481). In patients with stage II disease, the difference in survival rates between group A and B did not reach statistical significance (43% vs 86%, P=0.1678). However, the difference was significant between group A and B for stage III disease (77% vs 41%, P=0.0414).
Conclusions: We found the TS polymorphism to be a significant and independent prognostic factor for operable colorectal cancer. We think assay of the TS polymorphism can overcome the technical pitfalls of immunohistochemical staining and give more solid prognostic information in the treatment of colorectal cancer. J Korean Soc Coloproctol 2004;20:151-156
키워드
대장암;Thymidylate synthase 유전자 이형성;예후인자
olorectal cancer;Thymidylate synthase gene polymorphism;Prognostic factor
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