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

Abstract

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, 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.

Integrating Biological Advances Into the Clinical Management of Breast Cancer Related Lymphedema

“…Several germline alterations in genes involved at various levels in lymphangiogenesis have been documented in BCRL patients, suggesting a possible role for individual predisposition in the development of lymphedema following breast cancer therapy ( Table 1). These genes include lymphocyte cytosolic protein 2 (LCP2), spleen associated tyrosine kinase (SYK), endothelial cell adhesion proteins (i.e., promoters, growth factors, and their receptors), interleukins, and K-channel genes (50,(63)(64)(65)(66)(67)(68)(69)(70)(71)(72). Interestingly, these genes show recurrent somatic alterations in breast cancer, with a higher prevalence of gene copy-number alterations (CNAs) than somatic mutations (Figure 4).…”

“…Several potassium channel genes were found to be the target of SNPs in the setting of secondary lymphedema. These genes include potassium voltage-gated channel subfamilies A member 1 (KCNA1), J member 3 (KCNJ3), 2 (KCNJ6), and K member 3 (KCNK3) (71). In particular, KCNA1 is a transmembrane protein selective for potassium-positive ions; its functions are to shape the action potential and promote the return of the depolarized membrane to its resting state.…”

“…In particular, KCNA1 is a transmembrane protein selective for potassium-positive ions; its functions are to shape the action potential and promote the return of the depolarized membrane to its resting state. KCJN3 and KCJN6 are inward rectifying channels that act in an opposite way to voltage gated-channels, supporting the flow of positively charged potassium ions into the cell and stabilizing the resting membrane of cells (38,71). Finally, KCNK3 is another relevant tissue factor that contributes to the maintenance of the resting potential, giving rise to the background or outward leak potassiumpositive currents (38).…”

Manual Lymphatic Drainage Ccombined with Functional Exercise in the Treatment of Lymphedema After Modified Radical Mastectomy

“…China is now one of the countries of fastest growing incidence of breast cancer [2]. So far operation is still the major treatment for primary invasive breast cancer [3], and mastectomy is adopted by most in that it can remove the lesion, maximizing the possibility of curing the cancer. However, lymphedema is very likely to occur in the upper limb of the affected side because axillary lymph node dissection in mastectomy and radiotherapy for local lesion destroy the lymphatic vessel net.…”

Genome Sequencing Technologies and Nursing

“…This Nursing Research special issue on Omics in Nursing Science showcases nurse scientists conducting multi-omic research from various methods such as targeted candidate genes (Correa-Rodriguez, Rio-Valle & Blanca, 2017; Zahari et al,. 2017; Smoot et al, 2017; Han et al, 2017; Gillespie et al, 2017; Lin, Nunez, Johns & Shaio, 2017; Gonzales, Yu, & Shaio, 2017), pharmacogenomics (Aroke, Crawford, Dungan, 2017), proteomics (Voss, et al, 2017), epigenomics (Braid, Okrah, Shetty & Bravo, 2017), and the microbiome (Cong et al, 2017; Jordan et al, 2017; Ames, Ranucci, Moriyama & Wallen, 2017), and lastly, we provide an overview of the role of nurse scientists in genome sequencing here in this paper. We hope to inspire nurses to continue utilizing innovative omics approaches in their research, consider where the field of nursing research may be heading, and envision the use of multi-omic strategies as the basis for development of useful interventions and subsequent translation for nursing practice in the US and abroad.…”