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

Persistent pain after breast cancer surgery is common, and substantial individual variability exists in terms of its severity. Given their role in nociceptive transmission and our previous finding of an association with preoperative breast pain, we hypothesized that variations in potassium (K+) channel genes would be associated with persistent breast pain after breast cancer surgery. Therefore, the purpose of this study was to test for associations of single nucleotide polymorphisms (SNPs) and inferred haplotypes among 10 K+ channel genes and the occurrence of persistent breast pain after surgery. Growth mixture modeling was used to identify latent classes (i.e., subgroups) of patients with distinct trajectories of worst 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). Comparisons were made between the two largest classes (i.e., No Pain and Mild Pain). Compared to the No Pain group, patients in the Mild Pain group were younger (p<.01), poorer functioning (p<.05), had more lymph nodes removed (p=.02), more frequently had reconstruction at the time of surgery (p<.01), were pre-menopausal (p<.05), and had strange sensations in the breast prior to surgery (p<.001). Significant associations were found between variations in 6 genes [KCNA1 (n=1, p<.01), KCND2 (n=1, p<.05), KCNJ3 (n=6, all p<.05), KCNJ6 (n=10, all p<.05), KCNK9 (n=3, all p<.05) and KCNS1 (n=2, both p<.05)] and pain group membership. K+ channel gene variations and distinct demographic and clinical characteristics are associated with a novel phenotypic characterization of persistent breast pain after breast cancer surgery.