Smolarz Beata, Makowska Marianna, Samulak Dariusz, Michalska Magdalena M, Mojs Ewa, Wilczak Maciej, Romanowicz Hanna
Laboratory of Molecular Genetics, Department of Pathology, Institute of Polish Mother's Memorial Hospital, Rzgowska 281/289, 93-338, Lodz, Poland,
Clin Exp Med. 2015 May;15(2):151-7. doi: 10.1007/s10238-014-0284-7. Epub 2014 Apr 13.
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.
参与DNA同源重组修复(HRR)及维持基因组完整性的XRCC2和XRCC3基因在预防导致癌症的突变方面发挥着关键作用。本研究的目的是评估三阴性乳腺癌(TNBC)风险与编码HRR两种关键蛋白的基因多态性之间的关联:XRCC2基因的Arg188His(c. 563 G>A;rs3218536,Genbank登录号NT 007914)和XRCC3基因的Thr241Met(c. 722 C>T;rs861539,Genbank登录号NT 026437)。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对70例TNBC患者及70例年龄和性别匹配的非癌症对照者的XRCC2和XRCC3基因多态性进行了研究。在本研究中,发现XRCC2基因的Arg188His多态性与三阴性乳腺癌的发病率之间存在关联。188His等位基因和188His/His纯合变异增加了癌症风险。通过淋巴结转移程度和组织学分级评估,证实XRCC2基因的Arg188His和XRCC3基因的Thr241Met多态性与TNBC进展之间存在关联。总之,XRCC2基因的Arg188His和XRCC3基因的Thr241Met多态性可被视为女性人群三阴性乳腺癌的预测因素。