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. 2023 Apr;25(2):289-299.
doi: 10.1177/10998004221134684. Epub 2022 Oct 18.

A Pilot Study of Associations Between the Occurrence of Palpitations and Cytokine Gene Variations in Women Prior to Breast Cancer Surgery

Ying Sheng  1 , Janet S Carpenter  2 , Brenda J Smith  2 , Steven M Paul  3 , Michelle Melisko  3 , Javid Moslehi  3 , Jon D Levine  3 , Yvette P Conley  4 , Kord M Kober  3 , Christine Miaskowski  3
Affiliations

A Pilot Study of Associations Between the Occurrence of Palpitations and Cytokine Gene Variations in Women Prior to Breast Cancer Surgery

Ying Sheng et al. Biol Res Nurs. 2023 Apr.

Abstract

Objectives: Palpitations are common and have a negative impact on women's quality of life. While evidence suggests that inflammatory mechanisms may play a role in the development of palpitations, no studies have evaluated for this association in patients with breast cancer who report palpitations prior to surgery. The purpose of this pilot study was to evaluate for associations between the occurrence of palpitations and single nucleotide polymorphisms (SNPs) in genes for pro- and anti-inflammatory cytokines, their receptors, and transcriptional regulators.

Methods: Patients were recruited prior to surgery and completed a self-report questionnaire on the occurrence of palpitations. Genotyping of SNPs in cytokine genes was performed using a custom array. Multiple logistic regression analyses were done to identify associations between the occurrence of palpitations and SNPs in fifteen candidate genes.

Results: Of the 82 SNPs evaluated in the bivariate analyses, eleven SNPs in 6 genes were associated with the occurrence of palpitations. After controlling for functional status, the occurrence of back pain, and self-reported and genomic estimates of race/ethnicity, 3 SNPs in 3 different genes (i.e., interleukin (IL) 1-beta (IL1B) rs1143643, IL10 rs3024505, IL13 rs1295686) were associated with the occurrence of palpitations prior to surgery (all p ≤ .038).

Conclusions: While these preliminary findings warrant replication, they suggest that inflammatory mechanisms may contribute to the subjective sensation of palpitations in women prior to breast cancer surgery.

Keywords: breast cancer; cardio-oncology; cytokines; interleukins; menopausal symptoms; palpitations; single nucleotide polymorphisms.

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Conflict of interest statement

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSC reports consulting fees from the University of Wisconsin, consulting fees from Simumetrix, and scale licensing fees from Mapi. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Differences between the no palpitations and palpitation groups in the percentages of patients who were homozygous for the common allele or heterozygous or homozygous for the rare allele for each significant polymorphism. Values are plotted as unadjusted proportions with corresponding p-values. A – Differences between the no palpitations and palpitation 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 rs1143643 in interleukin (IL) 1-beta (IL1B). B – Differences between the no palpitations and palpitation groups in the percentages of patients who were homozygous for the common allele (CC), heterozygous for the rare allele (CT), or homozygous for the rare allele (TT) for rs3024505 in the IL10. C – Differences between the no palpitations and palpitation 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 rs1295686 in IL13.
Figure 2.
Figure 2.
Visualization of the genomic regions flanking the single nucleotide polymorphisms (SNPs) in this study. Evaluation of these genomic regions for potential regulatory roles can provide overlapping sources of evidence for a regulatory region for the DNA and SNPs. The genomic regions are presented flanking (A) IL1B rs1143643, (B) IL10 rs3024505, and (C) IL13 rs1295686. Each track of the figure presents data in the assembly coordinate system. The gene models are provided by the “RefSeq” track to show the location of the genes on the assembly. The study SNPs are labeled and identified by a vertical line and solid arrow. SNPs in high linkage disequilibrium with study SNPS are identified with a dotted arrow. SNPs are annotated by dbSNP release 153. To evaluate the potential regulatory roles for these SNPs, putative regulatory regions are identified by the “ENCODE” tracks. The “DNaseI Cluster” track identifies regions that are DNase-I sensitive, a characteristic of promoter regions. The “Enhanced H3K27Ac” track identifies regions where modifications of histone proteins were found and are suggestive of enhancer regulatory activity. The “Txn Factor ChIP” track shows where transcription factors bind. Visualization is provided by the University of California Santa Cruz Human Genome Browser (Version hg19).
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