Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor
cells, affects both children and adults, with peak prevalence between the ages of 2 and 5
years, and is the most common paediatric cancer. Genetic susceptibility to leukemias can
be related to the polymorphisms in multiple genes and consistent with this paradigm;
several polymorphisms have been identified in the pathogenesis of lymphoid
malignancies. The enzyme encoded by Thymidylate Synthase (TS) gene is a crucial
enzyme in the folate metabolism and plays an important role in the DNA synthesis and
repair pathway. Impairments in this enzyme have been associated with chromosome
breaks and fragile site induction, which in turn have been associated with the
development of lymphoid malignancies including leukemias. The aim of the study was to
investigate whether the tandem repeat polymorphism in the TS promoter region is a risk
factor for the development of acute lymphoblastic leukemia in Kashmiri population. The
repeat polymorphism in the TS gene was evaluated in 72 ALL cases and 82 (age, sex and
region matched, non malignant) controls by PCR analysis of DNA obtained from the
blood of the subjects and direct sequencing of the PCR products. We observed that the
TS triple tandem repeat (3R) allele frequency was 73.75 % in the controls and 67.91% in
cases. This difference in frequency was found to be statistically insignificant with a P =
0.2713(P> .05). The TS 2R/2R genotype was found to be present in 13.88% of the cases
and 9.75% of the controls, the 2R/3R variant in 31.94% of the cases and 31.70% of
controls, and the 3R/3R genotype in 47.22% of cases and 56.09% of controls.
We observed that although the proportion of patients who were homozygous for the TS
tandem repeat(3R/3R) was lower in cases than in controls, the difference was not
statistically significant when using 2R/2R genotype as a reference (OR= 0.5913; 95% CI,
0.2111-1.657; P = 0.3143). Similarly, we observed the frequency of the heterozygous
genotype (2R/3R) when compared with 2R/2R genotype was not much different between
the cases and controls hence, statistically insignificant (OR=0.7077; 95% CI, 0.2389-
2.097; P= 0.5317). Thus, our study suggests that there is no association between TS
tandem repeat polymorphism and the development of ALL in Kashmiri population.
However these findings need to be substantiated with larger sample size to clarify the real
contribution of this gene in the susceptibility to ALL in different world populations
