Article
The thymidylate synthase promoter polymorphism and prognosis in neoadjuvant treated and primarily resected advanced gastric cancer patients
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Published: | March 20, 2006 |
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Purpose: We evaluated DNA polymorphisms in the thymidylate synthase (TS) for an association with response and survival in locally advanced gastric cancer treated with primary resection or 5-FU based preoperative chemotherapy (CTx). Recently we found an association with prognosis, but not response in neadjuvant treated gaastric cancer.
Experimental Design: The DNA of 205 patients completely resected patients (102 with CTx; 103 without CTx) was isolated from blood or from nontumorous tissues. Genotyping of the tandem repeat polymorphism in the promoter region of the TS gene was performed by PCR.
Results: 53 (52%) of the patients with primary resection had the 2R/3R genotype, 28 (27%) the 3R/3R and 22 (21%) the 2R/2R genotype. 46 (45%) of the patients with neoadjuvant CTx showed the 2R/3R genotype, 29 (28%) the 3R/3R genotype and 27 (27%) the 2R/2R genotype (p=0.60). In the CTx-group, the TS genotypes were not associated with clinical (p=0.93) or histopathological response (p=0.71), but were significantly related to survival (Median survival in months: 3R/3R: 35,2; 2R/3R: n.e; 2R/2R: n.e.; p=0,003). In contrast there is no survival difference in the primary resected patients regarding the genotype (3R/3R: 33,3; 2R/3R: 47,6; 2R/2R: 32,0; p=0,83). Comparing survival between completely resected patients with and without CTx in the respective TS genotype groups, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n=49; p=0.002) and 2rpt/3rpt genotypes (n=99; p=0.004), but not for the 3rpt/3rpt genotype (n=57; p=0.93).
Conclusion: Our results show that patients` prognosis after CTx was associated with the TS genotype. Patients with the 3rpt/3rpt genotype did not benefit from CTx. Thus a different CTx or primary surgery might be more appropriate for these patients.