title: Variations in potassium channel genes are associated with distinct trajectories of persistent breast pain after breast cancer surgery.
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 10 potassium channel genes and persistent breast pain were evaluated. Using growth mixture modeling (GMM), 4 distinct latent classes of patients, who were assessed before and monthly for 6 months after breast cancer surgery, were identified previously (ie, 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 vs No Pain and Severe Pain vs No Pain classes. Seven single-nucleotide polymorphisms (SNPs) across 5 genes (ie, 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 and KCNJ6), potassium channel, subfamily K, member 9 [KCNK9]) were associated with membership in the Mild Pain class. In addition, 3 SNPs and 1 haplotype across 4 genes (ie, 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. Although findings from this study warrant replication, they provide intriguing preliminary information on potential therapeutic targets.
authors.affiliation: Schools of Nursing, University of California, San Francisco, CA, USA Schools of Medicine, University of California, San Francisco, CA, USA Institute for Human Genetics, University of California, San Francisco, CA, USA.
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Langford
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: Claudia M
authors.initials: CM
authors.lastname: West
authors.forename: Laura B
authors.initials: LB
authors.lastname: Dunn
authors.forename: Jon D
authors.initials: JD
authors.lastname: Levine
authors.forename: Kord M
authors.initials: KM
authors.lastname: Kober
authors.forename: Marylin J
authors.initials: MJ
authors.lastname: Dodd
authors.forename: Christine
authors.initials: C
authors.lastname: Miaskowski
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000601:surgery; D016009:Chi-Square Distribution; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008408:Mastectomy / Q000009:adverse effects*; D059373:Mastodynia / Q000209:etiology* / Q000235:genetics*; D008875:Middle Aged; D010147:Pain Measurement; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications / Q000235:genetics* / Q000503:physiopathology; D015221:Potassium Channels / Q000235:genetics*; D012044:Regression Analysis; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: D015221:Potassium Channels