Variations in inflammatory cytokine genes are associated with persistent severe breast pain after breast cancer surgery

Persistent pain following breast cancer surgery is a significant problem. Immune mechanisms appear to play a central role in the development and maintenance of persistent pain. Few studies have evaluated for associations between persistent breast pain following breast cancer surgery and variations in genes that encode for inflammatory cytokines. 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). The purpose of this study was to evaluate for associations between single nucleotide polymorphisms (SNPs) among 15 cytokine genes and persistent breast pain after surgery (i.e., No Pain GMM group and Severe Pain GMM group). Women in the Severe Pain group, compared to the No Pain group, differed on a number of demographic (i.e., age, years of education, income, ethnicity, comorbidities, functional status), pre-operative (i.e., pain in the breast prior to surgery), intraoperative (i.e., number of lymph modes removed), and post-operative (i.e., worst postoperative pain scores, re-excision or mastectomy within 6 months after surgery) characteristics (all p<0.05). After adjustment for severity of worst postoperative pain, three SNPs (i.e., interleukin (IL) 1 receptor 2: rs11674595; IL4 rs2243248; IL13: rs1800925) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of severe persistent pain following breast cancer surgery. These variations may help to identify patients who are predisposed to the development of severe persistent breast pain following breast cancer surgery.