TITLE:
Thymidylate Synthase 5’ UTR Polymorphic Allele Distribution in South Florida Population
AUTHORS:
Hiba Hammad, Malancha Sarkar, Pochi R. Subbarayan, Bach Ardalan
KEYWORDS:
TYMS Enhancer Region; Polymorphic Repeats; Translation Regulation; 5-FU Resistance; Colorectal Cancer
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.3 No.2,
April
24,
2012
ABSTRACT: Thymidylate synthase (TS; TYMS) is a pivotal enzyme in the DNA synthesis pathway. The 5’UTR of TYMS gene has a polymorphic 28 bp segment. Presence of two or three repeats of this unique 28 bp sequence is common. A distinct population distribution pattern for this polymorphic trait among different racial groups had been reported. We analyzed TYMS genotype in the peripheral blood mononucleocytes (PBMC) of 74 individuals in the South Florida region of the United States of America. The number of 28 bp repeats in the 5’ UTR was determined by PCR followed by agarose gel electrophoresis. The distribution of the three different genotypes was found to be 35.1% for 2R/2R, 39.2% for 2R/3R and 24.3% for 3R/3R. One individual was detected with 3R/4R genotype. Functional analyses associated homozygous for three repeats (3R/3R) to higher TYMS expression and therefore poor prognosis to chemotherapy. The other possible genotypes viz 2R/2R or 2R/3R is proposed to have better prognosis. However, there are reports that challenge this observation.