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首页> 外文期刊>Journal of Cancer Research and Treatment >Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort
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Impact of DNA Repair Genes Polymorphisms on Incidence and Prognosis of Breast Cancer in an Egyptian Cohort

机译：DNA修复基因多态性对埃及人群乳腺癌发病率和预后的影响

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Background: Sporadic breast cancer might be caused by low-penetrance genes, including genes constituting the DNA repair pathways. Defective DNA repair is a common imprint of cancer that promotes the accretion of DNA errors and genomic instability. The clustering of damage in DNA may stimulate breast carcinogenesis. Aims: The goal of the study is to evaluate the role of single nucleotide polymorphisms in DNA repair genes XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met as genetic indicators of susceptibility to breast cancer and to evaluate their role in treatment outcome. Methodology: The study included 248 females diagnosed with primary breast cancer and 232 normal healthy females. Patients were clinically followed up for 5 years after completing chemotherapy. Genomic DNA was isolated and the four polymorphisms under investigation were assessed by PCR-RFLP technique. Findings: XRCC1 399Gln, XPD 751Gln and XRCC3 241Met alleles were significantly associated with breast cancer risk (OR = 2.63, 2.17 and 3.21; respectively), with carriers having lower disease free survival (DSF). When grouping patients based on the number of affected genotypes they carry, DFS decreased as the number of affected genotypes increased (Paccum<0.001), patients carrying three (HR=4.74, p<0.001) or two (HR=3.35, p=0.005) affected genotypes had significantly worse DFS compared with those carrying zero (reference) or one (HR=1.37, p=0.093) affected genotype. RAD51 5’UTR G135C polymorphism was not associated with breast cancer risk (p=0.932) or with DFS. Conclusion: XRCC1 Arg399Gln, XPD Lys751Gln and XRCC3 Thr241Met polymorphisms may take a significant part in sporadic breast cancer as risk factors and in prognosis, where patients carrying XRCC1 Arg/Arg, XPD Lys/Lys and XRCC3 Thr/Thr genotypes had significantly diminished risk for breast cancer and higher DFS. DFS decreased as the number of affected genotypes increased. But RAD51 5'UTR G135C polymorphism did not associate with either risk or prognosis of breast cancer.
机译：背景：散发性乳腺癌可能是由低渗透基因（包括构成DNA修复途径的基因）引起的。有缺陷的DNA修复是癌症的常见印记，可促进DNA错误的积累和基因组不稳定。 DNA损伤的聚集可能会刺激乳腺癌的发生。目的：本研究的目的是评估单核苷酸多态性在DNA修复基因XRCC1 Arg399Gln，XPD Lys751Gln，RAD51 G135C和XRCC3 Thr241Met中的作用，作为乳腺癌易感性的遗传指标，并评估其在治疗结果中的作用。方法：该研究包括248位被诊断患有原发性乳腺癌的女性和232位正常健康的女性。完成化疗后，对患者进行了5年的临床随访。分离基因组DNA，并通过PCR-RFLP技术评估所研究的四个多态性。结果：XRCC1 399Gln，XPD 751Gln和XRCC3 241Met等位基因与乳腺癌风险显着相关（OR分别为2.63、2.17和3.21），且携带者的无病生存期较低（DSF）。当根据患者携带的受影响基因型的数量对患者进行分组时，DFS随受影响基因型数量的增加而降低（Paccum <0.001），携带三种（HR = 4.74，p <0.001）或两种（HR = 3.35，p = 0.005）的患者）受影响的基因型与携带零（参考）或一个（HR = 1.37，p = 0.093）受影响基因型的基因型相比，DFS明显更差。 RAD51 5’UTR G135C多态性与罹患乳腺癌的风险（p = 0.932）或DFS无关。结论：XRCC1 Arg399Gln，XPD Lys751Gln和XRCC3 Thr241Met多态性可能在散发性乳腺癌中作为危险因素和预后中的重要组成部分，其中携带XRCC1 Arg / Arg，XPD Lys / Lys和XRCC3 Thr / Thr基因型的患者显着降低了患病风险乳腺癌和更高的DFS。随着受影响基因型数量的增加，DFS下降。但是RAD51 5'UTR G135C多态性与乳腺癌的风险或预后均无关。

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