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乳腺癌中XPG基因多态性的临床结局洞察。

An insight into clinical outcome of XPG polymorphisms in breast cancer.

作者信息

Malik Saima Shakil, Mubarik Sumaira, Masood Nosheen, Khadim Muhammad Tahir

机构信息

Fatima Jinnah Women University, The Mall, Rawalpindi, 46000, Pakistan.

Armed Forces Institute of Pathology, Rawalpindi, Pakistan.

出版信息

Mol Biol Rep. 2018 Dec;45(6):2369-2375. doi: 10.1007/s11033-018-4401-7. Epub 2018 Sep 25.

Abstract

XPG polymorphisms are associated with varied clinical outcomes in different cancers but up-till now no study has been reported on breast cancer. Therefore, current study was aimed to explore the association of breast cancer risk factors and XPG polymorphisms (rs2296147 and rs1047768). It also investigated impact of XPG variants on overall survival and progression free survival among breast cancer cases. A total of 493 histopathologically identified breast cancer cases and 387 healthy females were genotyped by ARMS-PCR. Relationship between general characteristics, XPG polymorphisms and breast cancer risk was accessed by conditional logistic regression and illustrated by OR and 95% CI. Kaplan Meier test was applied to estimate survival distributions whereas log rank test demonstrated survival differences. Association of XPG variants with OS and PFS in breast cancer was illustrated by HR and 95% CI. Early onset of menopause, consanguinity and family history contributed (P < 0.05) towards breast cancer development. Both rs2296147 and rs1047768 SNPs were found to be associated (P < 0.05) with the risk of breast cancer. XPG rs1047768 was significantly associated with decreased PFS (HR 1.72; 95% CI 1.0-2.8) in breast cancer cases (P = 0.013) which was demonstrated by median time of 26 months for T > C variant when compared with median time of 37 months for TT genotype. No association was found between XPG rs2296147 polymorphism and survival analysis among breast cancer cases. XPG (rs1047768 T > C) variant may play a significant role in terms of decreased PFS and could be used as a predictor of unfavourable prognosis among breast cancer.

摘要

XPG基因多态性与不同癌症的多种临床结局相关,但迄今为止尚无关于乳腺癌的研究报道。因此,本研究旨在探讨乳腺癌危险因素与XPG基因多态性(rs2296147和rs1047768)之间的关联。同时,本研究还调查了XPG基因变异对乳腺癌患者总生存期和无进展生存期的影响。通过扩增阻滞突变系统聚合酶链反应(ARMS-PCR)对493例经组织病理学确诊的乳腺癌病例和387名健康女性进行基因分型。采用条件逻辑回归分析一般特征、XPG基因多态性与乳腺癌风险之间的关系,并以比值比(OR)和95%可信区间(CI)表示。应用Kaplan-Meier检验估计生存分布,对数秩检验显示生存差异。采用风险比(HR)和95%CI说明XPG基因变异与乳腺癌患者总生存期和无进展生存期的关联。绝经早、近亲结婚和家族史与乳腺癌发生有关(P<0.05)。发现rs2296147和rs1047768这两个单核苷酸多态性(SNP)均与乳腺癌风险相关(P<0.05)。XPG rs1047768与乳腺癌患者无进展生存期缩短显著相关(HR 1.72;95%CI 1.0 - 2.8)(P = 0.013),T>C变异型的中位时间为26个月,而TT基因型的中位时间为37个月。在乳腺癌病例中,未发现XPG rs2296147多态性与生存分析之间存在关联。XPG(rs1047768 T>C)变异可能在无进展生存期缩短方面起重要作用,可作为乳腺癌预后不良的预测指标。

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