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神经营养因子基因IVSI - 663多态性而非RET变异与乳腺癌风险增加相关。

Neurturin gene IVSI-663 polymorphism but not RET variants is associated with increased risk for breast cancer.

作者信息

Taşkan Tuba, Noori Farshad, Kurukahvecioğlu Osman, Karaman Niyazi, Gönenç Aymelek

机构信息

Afyonkarahisar Health Sciences University, Faculty of Pharmacy, Department of Biochemistry, Afyonkarahisar, Türkiye.

Chris O'brien Lifehouse Hospital, General Surgery Outpatient Clinic, Sydney, Australia.

出版信息

Lab Med. 2025 Jul 11;56(4):351-359. doi: 10.1093/labmed/lmae097.

Abstract

BACKGROUND

Gene polymorphisms of rearranged during transfection (RET) and its ligand neurturin (NRTN) are one of the focus of studies in the investigation of cancer pathogenesis, invasion, and metastasis. In this study, we aimed to examine the possible risk of breast cancer between RET G691S, L769L, S904S, and NRTN IVSI-663 polymorphisms and to evaluate serum NRTN, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase (FAK) levels.

METHODS

The study consists of 110 breast cancer patients and 110 controls. Polymorphisms were detected by the polymerase chain reaction method from study groups whole blood.

RESULTS

The NRTN IVSI-663 polymorphism in G allele has been found to be 1.54 fold increased the risk of breast cancer, however AA genotype has been found 0.43 fold decreased the risk of breast cancer (P < .05, P < .05, respectively). Study groups showed a similar profile for RET G691S, L769L, S904S allele frequencies and genotype distributions (P > .05). In the patient group, significant increase in serum NRTN and FAK levels and decrease in MMP-2 and MMP-9 levels were found (P < .05, P < .05, P < .05, P < .05, respectively).

DISCUSSION

In summary that increased breast cancer risk with the G allele in NRTN gene IVSI-663 polymorphism, as well as the increased serum NRTN and FAK levels, will contribute to the diagnosis, prognosis and determination of new treatment strategies.

摘要

背景

转染重排(RET)基因及其配体神经营养因子(NRTN)的基因多态性是癌症发病机制、侵袭和转移研究的重点之一。在本研究中,我们旨在探讨RET基因G691S、L769L、S904S多态性以及NRTN基因IVS1-663多态性与乳腺癌发生风险的关系,并评估血清NRTN、脑源性神经营养因子(BDNF)、基质金属蛋白酶(MMP)-2、MMP-9和粘着斑激酶(FAK)水平。

方法

本研究纳入110例乳腺癌患者和110例对照。通过聚合酶链反应法检测研究组全血中的多态性。

结果

发现NRTN基因IVS1-663多态性中G等位基因使乳腺癌风险增加1.54倍,而AA基因型使乳腺癌风险降低0.43倍(分别为P <.05,P <.05)。研究组在RET基因G691S、L769L、S904S等位基因频率和基因型分布方面表现出相似特征(P>.05)。在患者组中,发现血清NRTN和FAK水平显著升高,MMP-2和MMP-9水平降低(分别为P <.05,P <.05,P <.05,P <.05)。

讨论

综上所述,NRTN基因IVS1-663多态性中的G等位基因增加乳腺癌风险,以及血清NRTN和FAK水平升高,将有助于乳腺癌的诊断、预后评估及新治疗策略的确定。

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