| 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. |
