Heterozygote deficiency in thymidylate synthase enhancer region polymorphism genotype distribution in Hungarian colorectal cancer patients

Vilmos Adleff, E. Hitre, I. Köves, Zsolt Orosz, Anna Hajnal, Judit Kralovánszky

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Thymidylate synthase (TS) gene polymorphisms are important as prognostic factors in cancer chemotherapy, but recent results describe that the TS enhancer region (TSER) polymorphic genotypes may also modulate risk for malignancies. Two functionally important and ethnically diverse polymorphisms are present on the TS transcript, TSER, a repeat polymorphism (2 or 3 repeats; 2R, 3R) affecting TS expression, and a 6 bp ins/del polymorphism on the 3′ UTR (position TS1494, del6 or ins6), which may influence mRNA stability. Hungarian population has one of the highest colorectal cancer (CRC) mortality rates in Europe, and several elevated dietary risk factors affect a large part of the population. In our study (99 primary CRC cases), population analysis of the patient group genotype frequencies revealed a departure from the Hardy-Weinberg equilibrium and significant heterozygote deficiency (p <0.05) at the TSER locus. Despite the strong linkage between the 2 polymorphic loci, case TS1494del genotype frequencies were normally distributed, as well as the genotype frequencies of the healthy control population (n = 102), at both loci. Case-control comparison demonstrated a lower relative risk of TSER heterozygotes (OR = 0.47; CI = 0.27-0.83; p = 0.008) and a possible higher prevalence of the 3R3R&ins6/del6 in the CRC group. The observation that heterozygotes are those less susceptible for CRC in the Hungarian population may support the possibility of 2 different pathways in which TS may play a role in colorectal carcinogenesis, probably nutrient (or folate)-dependently. The lack of similar genotype effect seen with TS1494del polymorphism and the increased presence of one genotype combination (3R3R&ins6/del6) in the patient group suggest a possible TS haplotype effect influencing CRC risk.

Original languageEnglish
Pages (from-to)852-856
Number of pages5
JournalInternational Journal of Cancer
Volume108
Issue number6
DOIs
Publication statusPublished - Mar 1 2004

Fingerprint

Thymidylate Synthase
Heterozygote
Colorectal Neoplasms
Genotype
Population
RNA Stability
3' Untranslated Regions
Folic Acid
Haplotypes
Neoplasms
Carcinogenesis
Drug Therapy
Food
Mortality
Genes

Keywords

  • Cancer risk
  • Colon cancer
  • Genetic polymorphism
  • Hungary
  • Population genetics
  • Thymidylate synthase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Heterozygote deficiency in thymidylate synthase enhancer region polymorphism genotype distribution in Hungarian colorectal cancer patients. / Adleff, Vilmos; Hitre, E.; Köves, I.; Orosz, Zsolt; Hajnal, Anna; Kralovánszky, Judit.

In: International Journal of Cancer, Vol. 108, No. 6, 01.03.2004, p. 852-856.

Research output: Contribution to journalArticle

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