Article

Variations in Potassium Channel Genes Are Associated With Breast Pain in Women Prior to Breast Cancer Surgery

Journal of neurogenetics (Impact Factor: 1.38). 01/2014; 28(1-2). DOI: 10.3109/01677063.2013.856430
Source: PubMed

ABSTRACT 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.

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    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.
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