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. 2017 Mar/Apr;66(2):85-94.
doi: 10.1097/NNR.0000000000000203.

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

Betty Smoot  1 , Kord M Kober, Steven M Paul, Jon D Levine, Gary Abrams, Judy Mastick, Kimberly Topp, Yvette P Conley, Christine A Miaskowski
Affiliations

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

Betty Smoot et al. Nurs Res. 2017 Mar/Apr.

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, 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.

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Conflict of interest statement

The authors have no conflicts of interest to report.

Figures

FIGURE 1
FIGURE 1
Differences between the lymphedema and no lymphedema groups. Panel A shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous or heterozygous for the common allele (CC+CT) or homozygous for the rare allele (TT) for rs4766311 in KCNA1. Panel B shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (GG) or heterozygous or homozygous for the rare allele (GA+AA) for rs1037091 in KCNJ3. Panel C shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (TT) or heterozygous or homozygous for the rare allele (TC+CC) for rs2211845 in KCNJ6. Panel D shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous or heterozygous for the common allele (CC+CA) or homozygous for the rare allele (AA) for rs991985 in KCNJ6. Panel E shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (CC) or heterozygous or homozygous for the rare allele (CT+TT) for rs2836019 in KCNJ6. Panel F shows differences between the lymphedema and no lymphedema groups in the percentages of patients who were homozygous for the common allele (CC) or heterozygous or homozygous for the rare allele (CT+TT) for rs1662988 in KCNJ3.
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