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儿茶酚-O-甲基转移酶(COMT)和神经营养酪氨酸激酶2(NTRK2)的变异影响接受乳腺癌治疗的女性的症状负担。

Variations in COMT and NTRK2 Influence Symptom Burden in Women Undergoing Breast Cancer Treatment.

作者信息

Young Erin E, Kelly Debra Lynch, Shim Insop, Baumbauer Kyle M, Starkweather Angela, Lyon Debra E

机构信息

1 Center for Advancement of Managing Pain, School of Nursing, University of Connecticut, Storrs, CT, USA.

2 Institute for Systems Genomics, UCONN Health, Farmington, CT, USA.

出版信息

Biol Res Nurs. 2017 May;19(3):318-328. doi: 10.1177/1099800417692877. Epub 2017 Feb 16.

Abstract

Women with breast cancer frequently report distressing symptoms during and after treatment that can significantly erode quality of life (QOL). Symptom burden among women with breast cancer is of complex etiology and is likely influenced by disease, treatment, and environmental factors as well as individual genetic differences. The purpose of the present study was to examine the relationships between genetic polymorphisms within Neurotrophic tyrosine kinase receptor 1 (NTRK1), Neurotrophic tyrosine kinase receptor 2 (NTRK2), and catechol-O-methyltransferase ( COMT) and patient symptom burden of QOL, pain, fatigue, anxiety, depression, and sleep disturbance before, during, and after treatment for breast cancer in a subset of participants ( N = 51) in a randomized clinical trial of a novel symptom-management modality for women with breast cancer undergoing chemotherapy. Patients were recruited at the time of initial breast cancer diagnosis and completed all survey measures at the time of recruitment, after the initiation of treatment (surgery and/or chemotherapy), and then following treatment conclusion. Multiple linear regression analyses revealed significant associations between NTRK2 and COMT single nucleotide polymorphism (SNP) genotype and symptom burden. Two COMT variants were associated with the specific symptoms of anxiety and QOL measures prior to the initiation of chemotherapy as well as pain interference and severity during and after treatment. Genotype at the NTRK2 SNP rs1212171 was associated with both sleep disturbance and fatigue. These findings, while exploratory, indicate that the genotypes of NTRK2 and COMT may contribute to relative risk for symptom burden during and shortly after the period of chemotherapy in women with early stage breast cancer.

摘要

乳腺癌患者经常报告在治疗期间及之后出现令人痛苦的症状,这些症状会显著降低生活质量(QOL)。乳腺癌女性的症状负担病因复杂,可能受疾病、治疗、环境因素以及个体基因差异的影响。本研究的目的是在一项针对接受化疗的乳腺癌女性的新型症状管理模式的随机临床试验的一部分参与者(N = 51)中,研究神经营养性酪氨酸激酶受体1(NTRK1)、神经营养性酪氨酸激酶受体2(NTRK2)和儿茶酚-O-甲基转移酶(COMT)内的基因多态性与患者在乳腺癌治疗前、治疗期间和治疗后的症状负担、生活质量、疼痛、疲劳、焦虑、抑郁和睡眠障碍之间的关系。患者在乳腺癌初次诊断时被招募,并在招募时、开始治疗(手术和/或化疗)后以及治疗结束后完成所有调查测量。多元线性回归分析显示NTRK2和COMT单核苷酸多态性(SNP)基因型与症状负担之间存在显著关联。两种COMT变体与化疗开始前的焦虑和生活质量测量的特定症状以及治疗期间和治疗后的疼痛干扰和严重程度相关。NTRK2 SNP rs1212171处的基因型与睡眠障碍和疲劳均相关。这些发现虽然具有探索性,但表明NTRK2和COMT的基因型可能导致早期乳腺癌女性在化疗期间及化疗后不久出现症状负担的相对风险增加。

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