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Polymorphisms of the DNA polymerase beta gene in breast cancer.

Abstract
DNA polymerase beta (Polbeta) provides most of the gap-filling synthesis at apurinic/apyrimidine sites of damaged DNA in the base excision repair pathway. Mutations in the gene encoding DNA polbeta have been identified in various carcinomas. We performed a case-control study to test the association between two polymorphisms in the polbeta gene: a Pro --> Arg change at codon 242 (the Pro242Arg polymorphism) and a Lys --> Met change at codon 289 (the Lys289Met polymorphism) and breast cancer risk and cancer progression. Genotypes were determined in DNA from peripheral blood lymphocytes of 150 breast cancer patients and 150 cancer-free, age-matched women (controls) by PCR-RFLP. A strong association between breast cancer occurrence and the Met/Met phenotype of the Lys289Met polymorphism [odds ratio (OR) 3.67; 95% confidence interval (CI) 1.87-7.56] and the Pro/Arg phenotype of the Pro242Lys polymorphism (OR 1.96; 95% CI 1.15-3.34) was found. Polymorphism-polymorphism interaction between the Met/Met phenotype of the Lys289Met and the Pro/Arg phenotype of the Pro242Arg variants increased the risk of breast cancer (OR 3.05; 95% CI 1.31-7.09). We did not observe any correlation between studied polymorphisms and breast cancer progression evaluated by node-metastasis, tumor size and Bloom-Richardson grading. In conclusion, Polbeta may play a role in the breast carcinogenesis and the Lys289Met polymorphism of the polbeta gene may be considered as an independent, early, molecular diagnostic marker in breast cancer. The Pro242Arg polymorphism may contribute to the carcinogenesis through the interaction with the Lys289Met and therefore may be regarded as a dependent, auxiliary marker.
AuthorsTomasz Sliwinski, Pawel Ziemba, Zbigniew Morawiec, Michal Kowalski, Marek Zadrozny, Janusz Blasiak
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 103 Issue 2 Pg. 161-6 (Jun 2007) ISSN: 0167-6806 [Print] Netherlands
PMID17131038 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA Polymerase beta
Topics
  • Breast Neoplasms (enzymology, genetics)
  • Case-Control Studies
  • DNA Polymerase beta (genetics)
  • Female
  • Humans
  • Middle Aged
  • Polymorphism, Genetic

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