P-191 - Exploration of the implication of thymidylate synthase polymorphisms on the risk of colorectal cancer in west Algerian population

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Rectal Cancer
Translational Research
Presenter M. Aberkane
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors M. Aberkane1, M.A. Loriot2
  • 1Faculty of Medicine University of Oran, Oran/DZ
  • 2Department Of Biochemistry, Pharmacogenetics And Molecular Oncology Unit, University Hospital HEGP, AP-HP, Paris/FR

Abstract

Introduction

Thymidylate synthase (TS) is a key enzyme in the biosynthesis of the thymidine which is required for the DNA synthesis and repair. It is also involved in folates metabolism known for their protective role against the colorectal cancer (CRC).

The aim of this study was to search for a possible relationship between the polymorphisms of TS (2R > 3R and del/ins 6pb) and the occurring of CRC in a population of 71 CRC and 48 healthy subjects from the west of Algeria.

Methods

The polymorphisms TS 2R > 3R and del/ins 6pb were assayed by a DNA fragment analysis (ABI PRISM 3700 DNA analysis - Applied Biosystems).

Results

An association between the polymorphism del/ins6pb of the TS gene and occurring of CRC was found in our population. Indeed, the individuals carrying insertion 6pb (allele 6pb) in TS gene had more risk to develop CRC than the individuals presenting the deletion of 6pb (allele 0pb) (OR = 1.92, p = 0.018). Moreover, a statistically significant difference was found between the cases and controls concerning the genotypes, suggesting that the two genotypes 0pb/6pb and 6pb/6pb are associated with a higher risk of CRC.

Conclusion

Our results suggest that the insertion of 6pb would be correlated with a lower activity of the TS increasing susceptibility to develop a CRC via a deficiency in the folates metabolism. Moreover, the deficit in thymine pool caused by the reduction of the rate of TS would probably lead the cell on a carcinogenesis way because of the uracil incorporation instead of the thymine in the DNA chain.