title: Thymidylate synthase enhancer region  polymorphism not related to susceptibility to acute lymphoblastic leukemia in the Kashmir population.
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 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.
authors.affiliation: Department of Biochemistry, University of Kashmir, Srinagar, India.
authors.forename: F H
authors.initials: FH
authors.lastname: Nazki
authors.forename: A
authors.initials: A
authors.lastname: Masood
authors.forename: M A
authors.initials: MA
authors.lastname: Banday
authors.forename: A
authors.initials: A
authors.lastname: Bhat
authors.forename: B A
authors.initials: BA
authors.lastname: Ganai
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D013940:Thymidylate Synthase / Q000235:genetics*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D013940:Thymidylate Synthase