The association of polymorphic markers Arg399Gln of XRCC1 gene, Arg72Pro of TP53 gene and T309G of MDM2 gene with breast cancer in Kyrgyz females

BMC Cancer. 2017 Nov 13;17(1):758. doi: 10.1186/s12885-017-3762-y.

Abstract

Background: The association of genes XRCC1, TP53 and MDM2 with breast cancer (BC) has never been tested in Kyrgyz population. We, therefore, aimed to identify an association of alleles and genotypes of polymorphic markers Arg399Gln of gene XRCC1, Arg72Pro of gene TP53, and T309G of gene MDM2 with the risk of BC in Kyrgyz women.

Methods: This was a case-control study of 219 women of Kyrgyz origin with morphologically verified BC (N = 117) and 102 controls, age-matched with BC cases. The mean age of subjects in this study was 52.2 ± 10.8 years. We extracted DNA from the venous blood and genotyped polymorphic markers Arg399Gln of gene XRCC1, Arg72Pro of gene TP53 and T309G of gene MDM2 using polymerase chain reaction and the method of restriction fragment polymorphism.

Results: Allele 399Gln (OR 1.57; 95% CI 1.05-2.35), Arg399Gln of gene XRCC1 heterozygous genotype (OR 2.77; 95% CI 1.60-4.80), the combination of Arg399Gln/Arg72Pro of genes XRCC1/TP53 heterozygous genotype (OR 3.98; 95% CI 1.57-10.09), Arg399Gln/T309G of genes XRCC1/MDM2 (OR 3.0; 95% CI 1.18-7.56), as well as Arg399Gln/Arg72Pro/T309G of genes XRCC1/TP53/MDM2 (OR 6.40; 95% CI 1.18-34.63) were associated with BC in Kyrgyz women.

Conclusions: This is the first study to identify the inter-loci interaction and to find molecular markers of individual risk of BC in Kyrgyz women.

Keywords: Breast cancer; Kyrgyz population; MDM2; TP53; XRCC1.

MeSH terms

  • Adult
  • Alleles
  • Amino Acid Substitution
  • Biomarkers, Tumor*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • Chromosome Mapping
  • Epistasis, Genetic
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Kyrgyzstan / epidemiology
  • Middle Aged
  • Neoplasm Grading
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins c-mdm2 / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • X-ray Repair Cross Complementing Protein 1 / genetics*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Protein p53
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Proto-Oncogene Proteins c-mdm2