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Potassium Channel Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery

Smoot, Betty; Kober, Kord M.; Paul, Steven M.; Levine, Jon D.; Abrams, Gary; Mastick, Judy; Topp, Kimberly; Conley, Yvette P.; Miaskowski, Christine A.

doi: 10.1097/NNR.0000000000000203
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Background Potassium (K+) channels play an important role in lymph pump activity, lymph formation, lymph transport, and the functions of lymph nodes. No studies have examined the relationship between K+ channel candidate genes and the development of secondary lymphedema (LE).

Objective The study purpose was to evaluate for differences in genotypic characteristics in women who did (n = 155) or did not (n = 387) develop upper extremity LE following breast cancer treatment based on an analysis of single-nucleotide polymorphisms (SNPs) and haplotypes in 10 K+ channel genes.

Methods Upper extremity LE was diagnosed using bioimpedance resistance ratios. Logistic regression analyses were used to identify those SNPs and haplotypes that were associated with LE while controlling for relevant demographic, clinical, and genomic characteristics.

Results Patients with LE had a higher body mass index, had a higher number of lymph nodes removed, had more advanced disease, received adjuvant chemotherapy, received radiation therapy, and were less likely to have undergone a sentinel lymph node biopsy. One SNP in a voltage-gated K+ channel gene (KCNA1 rs4766311), four in two inward-rectifying K+ channel genes (KCNJ3 rs1037091 and KCNJ6 rs2211845, rs991985, rs2836019), and one in a two-pore K+ channel gene (KCNK3 rs1662988) were associated with LE.

Discussion These preliminary findings suggest that K+ channel genes play a role in the development of secondary LE.

Betty Smoot, PT, DPTSc, MAS, is Associate Professor, School of Medicine, University of California San Francisco.

Kord M. Kober, PhD, is Assistant Professor; and Steven M. Paul, PhD, is Principal Statistician, School of Nursing, University of California San Francisco.

Jon D. Levine, MD, is Professor; and Gary Abrams, MD, is Professor, School of Medicine, University of California San Francisco.

Judy Mastick, RN, MN, is Project Director, School of Nursing, University of California San Francisco.

Kimberly Topp, PT, PhD, is Professor, School of Medicine, University of California San Francisco.

Yvette P. Conley, PhD, FAAN, is Professor, School of Nursing, University of Pittsburgh, Pennsylvania.

Christine Miaskowski, PhD, RN, FAAN, is Professor, School of Nursing, University of California San Francisco.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s web site (www.nursingresearchonline.com).

Accepted for publication August 19, 2016.

The authors acknowledge that this study was funded by grants from the National Cancer Institute (NCI; CA107091 and CA118658) and the National Institute of Nursing Research (NR0101282). Dr. Christine Miaskowski is an American Cancer Society Clinical Research Professor and is funded by a K05 award from the NCI (CA168960). This project was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

Editorial Note: Dr. Kathleen Hickey was Action Editor for this paper.

The authors have no conflicts of interest to report.

Corresponding author: Christine Miaskowski, PhD, RN, FAAN, School of Nursing, University of California San Francisco, 2 Koret Way, Room 631F, Box 0601, San Francisco, CA (e-mail: chris.miaskowski@ucsf.edu).

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