Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and triple-negative breast cancer in Polish women

Abstract

XRCC2 and XRCC3 genes involved in homologous recombination repair (HRR) of DNA and in the maintenance of the genome integrity play a crucial role in protecting against mutations that lead to cancer. The aim of the present work was to evaluate associations between the risk of triple-negative breast cancer (TNBC) and polymorphisms in the genes, encoding for two key proteins of HRR: XRCC2 Arg188His (c. 563 G>A; rs3218536, Genbank Accession Number NT 007914) and XRCC3 Thr241Met (c. 722 C>T; rs861539, Genbank Accession Number NT 026437). The polymorphisms of the XRCC2 and XRCC3 were investigated by PCR–RFLP in 70 patients with TNBC and 70 age- and sex-matched non-cancer controls. In the present work, a relationship was identified between XRCC2 Arg188His polymorphism and the incidence of triple-negative breast cancer. The 188His allele and 188His/His homozygous variant increased cancer risk. An association was confirmed between XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms and TNBC progression, assessed by the degree of lymph node metastases and histological grades. In conclusion, XRCC2 Arg188His and XRCC3 Thr241Met polymorphisms may be regarded as predictive factors of triple-negative breast cancer in female population.

Inhibition of FoxM1-Mediated DNA Repair by Imipramine Blue Suppresses Breast Cancer Growth and Metastasis

“…In addition to FoxM1-RAD51/Skp2 signaling cascade, XRCC3 is another gene that may mediate DNA repair events in IB-treated breast cancer cells as XRCC3 is known to participate in homologous recombination to maintain chromosome stability and repair DNA damage (23). Importantly, increase XRCC3 levels are associated with increased homologous recombination (25) and variants of XRCC3 was recently shown to be associated with increased risk for breast cancer patients (40). …”

Lack of Association between the 4234G/C X-Ray Repair Cross- Complementing 2 ( XRCC2 ) Gene Polymorphism and the Risk of Endometrial Cancer among Polish Population

“…The 188His allele and 188His/ His homozygous variant of XRCC2 Arg188His polymorphism were associated with increased risk of breast cancer in Polish population [7].…”

DNA repair and damage pathways in breast cancer development and therapy

“…Multiple genetic polymorphisms, especially single nucleotide polymorphisms (SNPs), have been recognized in genes involved in HR pathway (e.g., XRCC1, XRCC2, XRCC3, NBS1 and RAD51) that may confer genetic predisposition to disease and also affect the repair capacity of breast cancer patients to different extents [39][40][41][42][43][44][45].…”