Variations in Potassium Channel Genes Are Associated With Breast Pain in Women Prior to Breast Cancer Surgery
Journal of neurogenetics (Impact Factor: 1.27). 01/2014; 28(1-2). DOI: 10.3109/01677063.2013.856430
Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.
- [Show abstract] [Hide abstract]
ABSTRACT: Approximately 30% of women report pain in the affected breast prior to breast cancer surgery. The purpose of this secondary analysis of our prospective study was to determine how women who experienced both preoperative and persistent postsurgical breast pain (n=107) differed from women who did not report preoperative breast pain and did (n=158) or did not (n=122) experience persistent postsurgical breast pain. Differences in demographic and clinical characteristics were evaluated. Linear mixed effects (LME) modeling was used to evaluate for group differences in symptom severity, function, sensation, and quality of life (QOL) over time. Between-group differences in demographic and clinical characteristics as well as trajectories of shoulder function and QOL were identified. Women with both preoperative and persistent postsurgical breast pain were younger; were more likely to report swelling, strange sensations, hardness, and numbness in the affected breast prior to surgery; and were more likely to have reconstruction at the time of surgery. Women with both preoperative and persistent postsurgical breast pain had more biopsies in the prior year, more lymph nodes removed, and reported more severe acute postsurgical pain than women without preoperative breast pain. LME modeling revealed significant group effects for the majority of outcomes evaluated. Over the six months of the study, women with both preoperative and persistent postsurgical pain had persistently poorer shoulder flexion and physical well-being than women without preoperative breast pain. Investigations of the etiology and molecular mechanisms of preoperative breast pain, as well as interventions for this high risk group, are needed. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.Journal of Pain and Symptom Management 12/2014; 49(6). DOI:10.1016/j.jpainsymman.2014.11.292 · 2.80 Impact Factor
- Pain 01/2015; 156(3). DOI:10.1097/01.j.pain.0000460337.39223.d9 · 5.21 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Persistent pain after breast cancer surgery is a common clinical problem. Given the role of potassium channels in modulating neuronal excitability, coupled with recently published genetic associations with preoperative breast pain, we hypothesized that variations in potassium channel genes will be associated with persistent postsurgical breast pain. In this study, associations between ten potassium channel genes and persistent breast pain were evaluated. Using growth mixture modeling (GMM), four distinct latent classes of patients, who were assessed prior to and monthly for six months following breast cancer surgery, were identified previously (i.e., No Pain, Mild Pain, Moderate Pain, Severe Pain). Genotyping was done using a custom array. Using logistic regression analyses, significant differences in a number of genotype or haplotype frequencies were found between: Mild Pain versus No Pain and Severe Pain versus No Pain classes. Seven single nucleotide polymorphisms (SNPs) across five genes (i.e., potassium voltage-gated channel, subfamily A, member 1 (KCNA1), potassium voltage-gated channel, subfamily D, member 2 (KCND2), potassium inwardly-rectifying channel, subfamily J, members 3 and 6 (KCNJ3, KCNJ6), potassium channel, subfamily K, member 9 (KCNK9)) were associated with membership in the Mild Pain class. In addition, three SNPs and one haplotype across four genes (i.e., KCND2, KCNJ3, KCNJ6, KCNK9) were associated with membership in the Severe Pain class. These findings suggest that variations in potassium channel genes are associated with both mild and severe persistent breast pain after breast cancer surgery. While findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.Pain 01/2015; 156(3). DOI:10.1097/01.j.pain.0000460319.87643.11 · 5.21 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.