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.