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脂联素与生存素基因多态性在子宫内膜癌中的上位性相互作用。

Epistatic interaction between adiponectin and survivin gene polymorphisms in endometrial carcinoma.

作者信息

Aminimoghaddam Soheila, Shahrabi-Farahani Maryam, Mohajeri-Tehrani Mohammadreza, Amiri Parvin, Fereidooni Forozande, Larijani Bagher, Shafiee Gita, Amoli Mahsa M

机构信息

Department of Obstetrics and Gynecology, Firouzgar Clinical Research Development Center, Iran University of Medical Sciences, Tehran, Iran.

Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Pathol Res Pract. 2015 Apr;211(4):293-7. doi: 10.1016/j.prp.2014.11.012. Epub 2014 Nov 27.

Abstract

Adiponectin appears to play an important role in the development and progression of several obesity-related malignancies. Also, overexpression of survivin, an inhibitor of apoptosis protein, is associated with increased risk of cancers. The aim of this study was to investigate the association between two polymorphisms in the adiponectin gene and endometrial cancer (EC) risk. We also investigated whether epistasis between surviving and adiponectin gene polymorphisms are associated with EC risk in an Iranian population. The samples comprised formalin-fixed, paraffin-embedded tissue sections obtained from the archive of the pathology department, Imam-Khomeini Hospital and Firouzgar hospital. After DNA extraction the genotyping was performed using PCR-RFLP technique. Single nucleotide polymorphisms (SNPs) in adiponectin (rs1063539, rs2241766) and survivin (rs9904341) gene were evaluated in the study. The increased frequency of ADIPOQ rs1063539C allele (CC+CG genotype) was associated with decreased EC risk [OR: 0.39(0.17-0.90)]. Survivin rs9904341C allele (CC+CG genotype) was associated with increased EC risk [crude OR: 2.75(1.27-5.95), adjusted OR: 2.93(1.27-6.76)]. We observed an epistatic interaction between survivin rs9904341 CC+CG genotype and ADIPOQ rs1063539 GG genotype increasing the risk of EC compared to those with other genotypes [OR: 4.86(1.88-12.54), P=0.001]. Our findings indicate that adiponectin might have a modulatory effect on survivin role and function in EC, which requires further investigation.

摘要

脂联素似乎在几种与肥胖相关的恶性肿瘤的发生和发展中发挥重要作用。此外,凋亡抑制蛋白survivin的过表达与癌症风险增加有关。本研究的目的是调查脂联素基因中的两个多态性与子宫内膜癌(EC)风险之间的关联。我们还研究了survivin和脂联素基因多态性之间的上位性是否与伊朗人群的EC风险相关。样本包括从伊玛目-霍梅尼医院和菲鲁兹加尔医院病理科档案中获取的福尔马林固定、石蜡包埋组织切片。DNA提取后,使用PCR-RFLP技术进行基因分型。本研究评估了脂联素(rs1063539、rs2241766)和survivin(rs9904341)基因中的单核苷酸多态性(SNP)。ADIPOQ rs1063539C等位基因(CC + CG基因型)频率增加与EC风险降低相关[比值比(OR):0.39(0.17 - 0.90)]。Survivin rs9904341C等位基因(CC + CG基因型)与EC风险增加相关[粗OR:2.75(1.27 - 5.95),校正后OR:2.93(1.27 - 6.76)]。我们观察到survivin rs9904341 CC + CG基因型与ADIPOQ rs1063539 GG基因型之间存在上位性相互作用,与其他基因型相比,增加了EC风险[OR:4.86(1.88 - 12.54),P = 0.001]。我们的研究结果表明,脂联素可能对survivin在EC中的作用和功能具有调节作用,这需要进一步研究。

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