Thymidylate synthase enhancer region polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population

Abstract

ABSTRACT. Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. The most common polymorphism in TS is a unique double (2R) or triple (3R) 28-bp tandem repeat sequence in the enhancer region of the TS gene (TSER). This genetic variation in TSER has been widely investigated and has been implicated as a risk factor for the development of various cancers, including acute lymphoblastic leukemia. It has also been found to influence sensitivity to anti-cancer drugs, such as methotrexate. We evaluated this polymorphism in acute lymphoblastic leukemia patients in the Kashmir population. In order to determine whether a double (2R2R) versus a triple (3R3R) 28-bp tandem repeat in the TSER modulates risk for acute lymphoblastic leukemia, 72 acute lymphoblastic leukemia cases and 144 age and gender matched, unrelated healthy individuals from the Kashmir region of India were evaluated for this polymorphism by PCR and direct sequencing. We found the frequency of the TS 2R allele to be 32.6 and 26.0%, in cases and controls, respectively. The TS 2R/2R genotype was found to be present in 15.27% of the cases TSER polymorphism and susceptibility to ALL and 9.72% of the controls, the 2R/3R variant in 34.72% of the cases and 32.63% of the controls, and the 3R/3R genotype in 50.0% of the cases and 57.63% of the controls. There was a significant association between the TS 2R/2R genotype and gender of acute lymphoblastic leukemia patients with males harboring the 2R/2R genotype exhibiting a higher risk of developing acute lymphoblastic leukemia than females (P = 0.009) We concluded that the TSER polymorphism appears not to be a risk factor for susceptibility to acute lymphoblastic leukemia in the Kashmir population.

Genotype and allele frequencies of TYMS rs2790 A > G polymorphism in a Chinese paediatric population with acute lymphoblastic leukaemia

“…European populations also confirmed the interethnic differences in the distribution of the investigated polymorphism. 19 In the present study, the allele and genotype frequencies for the rs2790 A > G polymorphism in patients with ALL were similar to those in the Chinese samples of the 1000 Genomes Project, potentially indicating no significant effects of the studied polymorphism on the risk for ALL. The protective role of the rs34743033 3R allele was reported in a population which consisted of 71 adult patients with ALL.…”

“…18 However, no statistically significant association of rs34743033 polymorphism on the susceptibility to ALL was found in a Kashmir population. 19 In the present study, the allele and genotype frequencies for the rs2790 A > G polymorphism in patients with ALL were similar to those in the Chinese samples of the 1000 Genomes Project, potentially indicating no significant effects of the studied polymorphism on the risk for ALL. However, this finding needs validation in a well-designed case-control study.…”

The Pemetrexed-Containing Treatments in the Non-small Cell Lung Cancer, Is -/Low Thymidylate Synthase Expression Better than +/High Thymidylate Synthase Expression? A Meta-analysis

“…IHC detects TS expression at protein level, while RT-PCR assays at mRNA level. Several studies have reported some discrepancy between mRNA expression and protein expression for TS [24,39,40]. A recent research by Hou.et.al found that very high protein expression of TS determined by IHC correlates well with TS mRNA expression, while low protein expression of TS correlates poorly with TS mRNA expression [41].…”

Prevalence of thymidylate synthase gene 5'-untranslated region variants in an Argentinean sample

“…However, no association has been established between the TYMS 5'-UTR VNTR polymorphism and the incidence of gastric tumors, breast cancer, or leukemia (Nazki et al, 2012;Quintero-Ramos et al, 2014;Araújo et al, 2015).…”