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.

Highlights

  • The term triple-negative breast cancer (TNBC) defines breast tumors that do not express estrogen receptors, progesterone receptor, or epidermal growth factor receptor HER2 on immunohistochemical analysis

  • 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

  • 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

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Summary

Introduction

The term triple-negative breast cancer (TNBC) defines breast tumors that do not express estrogen receptors, progesterone receptor, or epidermal growth factor receptor HER2 on immunohistochemical analysis. TNBC refers to about 15–20 % of all breast cancer cases [1,2,3,4,5]. Molecular profiling indicated that triple-negative breast cancer represents heterogeneous subgroup of breast cancer. Triple-negative breast cancer shares histological and genetic abnormalities with basal-like subtype of breast cancer, this overlap is incomplete. Triple-negative breast cancer do not benefit from hormonal therapies or treatments targeted against HER2 [1,2,3,4,5]. Many of targeted therapeutic agents show promise in early stage studies, but their clinical performance has yet to be definitively proven

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