Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Mar-Jun;28(1-2):122-35.
doi: 10.3109/01677063.2013.856430. Epub 2014 Jan 7.

Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery

Dale J Langford  1 , Claudia West, Charles Elboim, Bruce A Cooper, Gary Abrams, Steven M Paul, Brian L Schmidt, Jon D Levine, John D Merriman, Anand Dhruva, John Neuhaus, Heather Leutwyler, Christina Baggott, Carmen Ward Sullivan, Bradley E Aouizerat, Christine Miaskowski
Affiliations

Variations in potassium channel genes are associated with breast pain in women prior to breast cancer surgery

Dale J Langford et al. J Neurogenet. 2014 Mar-Jun.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
KCNJ3 linkage disequilibrium-based heatmap and haplotype analysis. An ideogram of potassium inwardly-rectifying channel, subfamily J, member 3 (KCNJ3, GIRK1, Kir3.1) is presented above the white bar that represents the physical distance along human (chromosome 2 position 155555093 to 155714864; genome build 37.10, NC_000002.11). Exons are represented as boxes. Gray lines connecting the exons represent introns. The direction of transcription is from left to right. Reference sequence identifiers (rsID) for each single nucleotide polymorphism (SNP) are plotted both in terms of their physical distance (i.e., the white bar at the top of the figure) and equidistantly in order to render the pairwise linkage disequilibrium (LD) estimates that were calculated and visualized with Haploview 4.2. The gene structure for KCNJ3 (i.e., hg18 NM_002239) was rendered with FancyGene 1.4. The correlation statistics (r2 and D’) are provided in the heatmap. LD-based haplotype block definition was based on D’ confidence interval (Conde et al., 2006a). The haploblock is outlined in a bolded triangle and its component SNPs are rendered in bold font. Pairwise D’ values (range: 0-1, inclusive) were rendered in greyscale, with dark grey diamonds representing D’ values approaching 1.0. When the r2 values (range of 0-100, inclusive) are not equal to 0 or 100, they are provided in a given diamond. The haplotypes i.e., HapE1-HapE4) observed in the haploblock 5 (i.e., “Block 5” indicated by the vertical black arrow in the figure) are listed in each row, starting with the nucleotide composition across the two SNPs that compose the haplotype (i.e., rs2591168, rs2591172) and the count frequency (%) of each haplotype observed in the no preoperative breast pain and preoperative breast pain groups. #The haplotype E1, composed of the “A” common allele at rs2591168 and the “G” rare allele at rs2591172, identified in the bivariate analyses (Table 1) remained significant after controlling for relevant covariates.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Alloui A, Zimmermann K, Mamet J, Duprat F, Noel J, Chemin J, et al. TREK-1, a K+ channel involved in polymodal pain perception. EMBO J. 2006;25:2368–2376. - PMC - PubMed
    1. Blednov YA, Stoffel M, Alva H, Harris RA. A pervasive mechanism for analgesia: activation of GIRK2 channels. Proc Natl Acad Sci U S A. 2003;100:277–282. - PMC - PubMed
    1. Brunner F, Bachmann LM, Weber U, Kessels AG, Perez RS, Marinus J, et al. Complex regional pain syndrome 1--the Swiss cohort study. BMC Musculoskelet Disord. 2008;9:92. - PMC - PubMed
    1. Conde L, Vaquerizas JM, Dopazo H, Arbiza L, Reumers J, Rousseau F, et al. PupaSuite: finding functional single nucleotide polymorphisms for large-scale genotyping purposes. Nucleic Acids Res. 2006;34:W621–625. - PMC - PubMed
    1. Corry DC. Pain in carcinoma of the breast. Lancet. 1952;1:274–276. - PubMed

Publication types

Substances