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首页> 外文学位 >Associations between Genetic and Epigenetic Variations in Cytokine Genes and Persistent Breast Pain after Breast Cancer Surgery.
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Associations between Genetic and Epigenetic Variations in Cytokine Genes and Persistent Breast Pain after Breast Cancer Surgery.

机译：乳腺癌手术后细胞因子基因的遗传和表观遗传变异与持续性乳房疼痛之间的关联。

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摘要

Persistent pain following breast cancer surgery is a significant clinical problem. Both inherited and acquired inflammatory factors (e.g., cytokines) appear to play a role in the development and maintenance of persistent pain. However, less is known about the molecular mechanisms of inflammation associated with the development of persistent pain following breast cancer surgery. Growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for six months following breast cancer surgery. The purpose of this dissertation is to evaluate for differences in demographic and clinical characteristics as well as to evaluate the associations between single nucleotide polymorphisms contained within candidate cytokine genes and pain group membership. In addition, methylation of the promoter region of the genes that harbored gene variations associated with pain group membership were evaluated in the no pain and mild pain classes. Different subsets of phenotypic characteristics (i.e., age, strange sensations prior to surgery, reconstruction performed at the time of surgery, re-excision/mastectomy done within six months and worst postoperative pain intensity) and genes (i.e., interleukin (IL) 1 receptor 2, IL4, IL10, IL13 and IL6, tumor necrosis factor alpha (TNFA)) were associated with the distinct phenotypes (i.e., mild persistent pain, severe persistent pain) and suggest that different mechanisms of heritable susceptibility may exist. In addition, CpG methylation within the TNFA promoter may provide an additional mechanism through which TNFA may alter the risk for mild persistent breast pain after breast cancer surgery. Coupled with phenotypic variations, these genetic and epigenetic variations may help to identify individuals who are predisposed to the development of persistent breast pain following breast cancer surgery, differentiate biological mechanisms, and facilitate the development of novel therapies.
机译：乳腺癌手术后的持续疼痛是一个重大的临床问题。遗传性和获得性炎性因子（例如细胞因子）似乎都在持续性疼痛的发展和维持中起作用。然而，关于乳腺癌手术后与持续性疼痛发展相关的炎症分子机制知之甚少。根据乳腺癌手术之前和之后六个月每月获得的疼痛评估，使用生长混合物建模来识别持续性乳房疼痛表型。本文的目的是评估人口统计学和临床​​特征的差异，以及评估候选细胞因子基因中包含的单核苷酸多态性与疼痛组成员之间的联系。另外，在无痛和轻度疼痛类别中评估了具有与疼痛组成员有关的基因变异的基因的启动子区域的甲基化。表型特征（例如年龄，手术前的奇怪感觉，手术时进行的重建，在六个月内进行的再次切除/乳房切除术以及术后最严重的疼痛强度）的不同子集和基因（即白介素（IL）1受体）如图2所示，IL4，IL10，IL13和IL6，肿瘤坏死因子α（TNFA）与不同的表型相关（即轻度持续性疼痛，严重持续性疼痛），提示可能存在遗传敏感性的不同机制。另外，TNFA启动子内的CpG甲基化可以提供另外的机制，通过该机制，TNFA可以改变乳腺癌手术后轻度持续性乳房疼痛的风险。结合表型变异，这些遗传和表观遗传变异可以帮助鉴定在乳腺癌手术后易患持续性乳房疼痛的个体，区分生物学机制，并促进新疗法的发展。

著录项

  • 作者

    Stephens, Kimberly.;

  • 作者单位

    University of California, San Francisco.;

  • 授予单位 University of California, San Francisco.;
  • 学科 Biology Neuroscience.;Health Sciences Nursing.;Biology Genetics.
  • 学位 Ph.D.
  • 年度 2013
  • 页码 176 p.
  • 总页数 176
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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