Variations in potassium channel genes are associated with severe persistent breast pain after breast cancer surgery

Persistent pain after breast cancer surgery is common with prevalence rates that range from 25% to 80%. Recently, we used growth mixture modeling to identify latent classes (i.e., subgroups) of patients with distinct trajectories of worst breast pain scores using a 0-10 numeric rating scale (NRS), reported prior to and monthly for 6 months after surgery. Four subgroups were identified: 126 patients (31.7%) with "No Pain", 173 (43.4%) with "Mild Pain" (NRS of ∼3 that remained constant), 53 (13.3%) with "Moderate Pain" (NRS of ∼2 that increased over time), and 46 (11.6%) with "Severe Pain" (NRS of ∼8 that remained constant). Given their role in nociceptive transmission, we previously identified associations between preoperative, post-operative, and persistent mild pain in the breast (i.e., Mild Pain GMM group) with variations in a number of potassium (K+) channel genes. The purpose of this study was to test for associations between single nucleotide polymorphisms (SNPs) in 10 K+ channel genes and severe persistent breast pain after surgery (i.e., Severe Pain GMM group). Compared to the No Pain group, patients in the Severe Pain group differed in several demographic (i.e., age, years of education, ethnicity, annual income), clinical (i.e., functional status, number of comorbidities, pain in the breast prior to surgery), intraoperative (i.e., number of lymph nodes removed, axillary lymph node dissection, and post-operative (i.e., severity of average and worst post-operative pain, re-excision or mastectomy during the 6 months following surgery) characteristics (all p<0.05). Significant associations were found between variations in 5 genes [KCND2 (n=4, p<.05), KCNJ3 (n=8, all p<.05), KCNJ6 (n=3, all p<.05), KCNK3 (n=2, all p<.05) and KCNK9 (n=1, p<.05)] and pain group membership. K+ channel gene variations and specific demographic and clinical characteristics are associated with a novel phenotypic characterization of persistent severe breast pain after breast cancer surgery.