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Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment

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Abstract

In our study, we investigate the possible association of thymidylate synthase polymorphism, 28 bp tandem repeat in 5′-UTR (transcription enhancer element) with susceptibility of colorectal and gastric cancer in Tunisian population. Because thymidylate synthase provides an effective prediction of chemotherapy treatment based on 5-fluorouracil, our interest in this study was focused on finding an eventual interaction between thymidylate synthase polymorphism and treatment of sporadic colorectal and gastric cancer. Whole blood was collected into EDTA tube, after centrifugation for 15 min, the buffy coat was isolated, and genotyping of TS 5′-UTR polymorphism was carried by polymerase chain reaction method using appropriate primers. Determination of the different genotypes was done directly on the stained agarose gel. Our finding showed that the 5′tandem repeat polymorphism of the thymidylate synthase gene is associated with risk of colorectal cancer; thus, LL (3R/3R) genotype is significantly high in patients with colorectal cancer compared to controls (P = 0.002; OR 2.7; 95 % CI 1.4–5.2). In addition, we found a positive association between SL (2R/3R) genotype in the thymidylate synthase 5′-UTR and gastric cancer risk (P = 0.015; OR 4.46; 95 % CI 1.08–19.64). Furthermore, we found a correlation of thymidylate synthase polymorphism with the fluorouracil-based therapy regimes and also with preoperatory radiation in patients with colorectal cancer. Thymidylate synthase is associated with risk of colorectal cancer but not with gastric cancer; however, heterozygous SL (2R/3R) polymorphism is associated with risk of gastric cancer; moreover, the 5′ tandem repeat polymorphism of thymidylate synthase gene was an independent predictor of the clinical treatment.

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Abbreviations

TS:

Thymidylate synthase

CRC:

Colorectal cancer

GC:

Gastric cancer

UTR:

Untranslated region

5FU:

5-Fluorouracil

VNTR:

Variable number tandem repeat

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Acknowledgments

The authors are grateful to the Laboratory of Genetics, Immunology and Human Pathology, Faculty of science Tunis El Manar University campus in 2092 Tunisia, Tunis. We are grateful to Professor Amel Benammar El-Gaaied for her advices and suggestions.

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There is no conflict between the authors.

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Correspondence to Olfa Baroudi.

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Baroudi, O., Baroudi, T., Omrane, I. et al. Thymidylate synthase polymorphism in sporadic colorectal and gastric cancer in Tunisian population: a predictive role in 5-fluorouracil based chemotherapy treatment. Med Oncol 31, 825 (2014). https://doi.org/10.1007/s12032-013-0825-z

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  • DOI: https://doi.org/10.1007/s12032-013-0825-z

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