Associations between cytokine gene variations and self-reported sleep disturbance in women following breast cancer surgery

Abstract

Purpose of the research To attempt to replicate the associations found in our previous study of patients and family caregivers between interleukin 6 (IL6) and nuclear factor kappa beta 2 (NFKB2) and sleep disturbance and to identify additional genetic associations in a larger sample of patients with breast cancer. Methods and sample Patients with breast cancer (n=398) were recruited prior to surgery and followed for six months. Patients completed a self-report measure of sleep disturbance and provided a blood sample for genomic analyses. Growth mixture modeling was used to identify distinct latent classes of patients with higher and lower levels of sleep disturbance. Key results Patients who were younger and who had higher comorbidity and lower functional status were more likely to be in the high sustained sleep disturbance class. Variations in three cytokine genes (i.e., IL1 receptor 2 (IL1R2), IL13, NFKB2) predicted latent class membership. Conclusions Polymorphisms in cytokine genes may partially explain inter-individual variability in sleep disturbance. Determination of high risk phenotypes and associated molecular markers may allow for earlier identification of patients at higher risk for developing sleep disturbance and lead to the development of more targeted clinical interventions.

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…However, these findings could not be replicated in a later report which evaluated the association among breast cancer patients only [61]. In contrast, a subsequent similar study on breast cancer patients by Miaskowski et al [103] demonstrated that NFKB2 (rs1056890) carriers had decreased odds of being classified in the high sustained sleep disturbance class, while carriers of the IL13 (rs1800925) SNP IL1R2 HapA2 haplotype (rs11674595, rs7570441) had increased odds of having a high sustained sleep disturbance. The fact that no association could be established between IL13 and sleep disturbance among oncology patients and their family care givers [102] warrants additional multi-centre studies to delineate the specific role of cytokines in predicting sleep disturbance among cancer patients including breast cancer.…”

Phenotypic and Molecular Evidence Suggests That Decrements in Morning and Evening Energy Are Distinct but Related Symptoms

“…Previously, we identified an association between sleep disturbance and variations in NFKB2 in both the current (rs7897947) 14 and an independent sample (rs1056890). 80 In both of these studies, being homozygous or heterozygous for the rare allele was associated with less sleep disturbance. These inconsistent findings warrant confirmation in future studies.…”

Inflammatory pathway genes associated with inter-individual variability in the trajectories of morning and evening fatigue in patients receiving chemotherapy

“…Consistent with our previous studies [14, 63, 77–80], recommendations from the literature [81, 82], rigorous quality controls for genomic data and the exploratory nature of our analyses, adjustments were not made for multiple testing. Since significant SNPs and liability scores identified in the exploratory analysis were evaluated further in the HLM analyses that controlled for population stratification (i.e., genomic and self-reported estimates of race and ethnicity), and other variations in the same gene, the significant independent genetic associations reported are unlikely to be due solely to chance.…”

“…Some of the details of the phenotypic [9–11, 62] and genotypic [63, 64] methods used in this study are published elsewhere. In brief, patients were recruited from two comprehensive cancer centers, one Veteran’s Affairs hospital, and four community-based oncology programs.…”