Persistent
pain following
breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of
inflammation appear to play a role in the development and maintenance of persistent
pain. In this longitudinal study, growth mixture modeling was used to identify persistent
breast pain phenotypes based on
pain assessments obtained prior to and monthly for 6months following
breast cancer surgery. Associations between the "no
pain" and "mild
pain" phenotypes and single nucleotide polymorphisms (SNPs) spanning 15
cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with
pain group membership was determined using
bisulfite sequencing. In the multivariate analysis, three SNPs (i.e.,
interleukin 6 (
IL6) rs2069840, C-X-C motif
chemokine ligand 8 (CXCL8) rs4073,
tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated with
pain group membership. These findings suggest that variations in
IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent
breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent
breast pain after
breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent
breast pain following
breast cancer surgery.