Associations Between Cytokine Gene Variations and Severe Persistent Breast Pain in Women Following Breast Cancer Surgery

Abstract

Persistent pain following breast cancer surgery is a significant clinical problem. While immune mechanisms may play a 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 cytokine genes. In this study, associations between previously identified extreme persistent breast pain phenotypes (i.e., no pain versus severe pain) and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. In unadjusted analyses, the frequency of 13 SNPs and 3 haplotypes in 7 genes differed significantly between the no pain and severe pain classes. After adjustment for preoperative breast pain and the severity of average postoperative pain, one SNPs (i.e., interleukin (IL) 1 receptor 2 rs11674595) and one haplotype (i.e., IL10 haplotype A8) were associated with pain group membership. These findings suggest a role for cytokine gene polymorphisms in the development of persistent breast pain following breast cancer surgery. Perspective This study evaluated for associations between cytokine gene variations and the severity of persistent breast pain in women following breast cancer surgery. Variations in two cytokine genes were associated with severe breast pain. The results suggest that cytokines play a role in the development of persistent postsurgical pain.

Genetic polymorphisms in IL1R1 and IL1R2 are associated with susceptibility to thyroid cancer in the Chinese Han population

“…Research on persistent pain in breast cancer revealed that the variation of rs11674595 was correlated with severe pain, which could be conducive to the prognosis analysis of breast cancer. 38 In combination with the results obtained in the present study, susceptibility to disease or syndromes could be ascribed to the dysregulation of IL1R2 resulting from the polymorphic SNPs (rs2072472 and rs11674595).…”

“…Rs2072472 has been demonstrated in ankylosing spondylitis and endometriosis for Northern Chinese Han and Korean women, respectively whereas no significant associations were observed with respect to the risk of disease. Research on persistent pain in breast cancer revealed that the variation of rs11674595 was correlated with severe pain, which could be conducive to the prognosis analysis of breast cancer . In combination with the results obtained in the present study, susceptibility to disease or syndromes could be ascribed to the dysregulation of IL1R2 resulting from the polymorphic SNPs (rs2072472 and rs11674595).…”

Genetic insights toward improved management of chronic pain after mastectomy

“…Supporting this, a separate study in the same cohort concluded that persistent breast pain is associated with genetic variation in inflammatory cytokines/receptors such as IL-1R and IL-10. 27 Together, these data raise the possibility of unidentified interactions between these inflammatory components and K 1 (or other ion) channels to establish a hyperexcitable phenotype, circumstantial evidence of which is already found in the literature. 5,8,28 Since analysis was limited to a small selection of genes, it would be informative to interrogate the involvement of additional K 1 channels, such as Kv7 channels that are known to be directly modulated by inflammatory agents.…”

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…A similar study conducted among breast cancer women following surgery (postoperatively) [118] demonstrated that carriers of IL1R2 (rs11674595) had higher odds of developing a severe persistent breast pain while those harbouring the IL10 haplotype A8 (made up of seven SNPs i.e. rs3024505, rs3024498, rs3024496, rs1878672, rs1518111, rs1518110, rs3024491) had decreased odds of having severe persistent breast pain.…”