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

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.

Keywords::

• breast cancer
• breast pain
• candidate genes
• potassium channel genes
• preoperative pain

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was funded by grants from the National Cancer Institute (CA107091 and CA118658). Dr. Miaskowski is an American Cancer Society (ACS) Clinical Research Professor. Dr. Dhruva is funded through NIH Mentored Patient-Oriented Research Career Development Award (K23 AT005340). Dr. Langford is supported by a Department of Defense Breast Cancer Research Program Postdoctoral Fellowship. Dr. Merriman was supported by an NINR fellowship (F31 NR012604), an ACS Doctoral Degree Scholarship (DSCN-10-087), an Oncology Nursing Society Doctoral Scholarship, and a UCSF Nursing Alumni Association Scholarship. Dr. Baggott is funded by an American Cancer Society Mentored Research Scholar Award (MRSG 12-01-PCSM). Dr. Leutwyler is funded by the KL2 Program (RR624130). Ms. Ward Sullivan is supported by an NINR T32. This project is supported by NIH/NCRR UCSF-CTSI grant UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.