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

Abstract

Fatigue, a highly prevalent and distressing symptom during chemotherapy (CTX), demonstrates diurnal and interindividual variability in severity. Little is known about the associations between variations in genes involved in inflammatory processes and morning and evening fatigue severity during CTX. The purposes of this study, in a sample of oncology patients (N=543) with breast, gastrointestinal (GI), gynecological (GYN), or lung cancer who received two cycles of CTX, were to determine whether variations in genes involved in inflammatory processes were associated with inter-individual variability in initial levels as well as in the trajectories of morning and evening fatigue. Patients completed the Lee Fatigue Scale to determine morning and evening fatigue severity a total of six times over two cycles of CTX. Using a whole exome array, 309 single nucleotide polymorphisms among the 64 candidate genes that passed all quality control filters were evaluated using hierarchical linear modeling (HLM). Based on the results of the HLM analyses, the final SNPs were evaluated for their potential impact on protein function using two bioinformational tools. The following inflammatory pathways were represented: chemokines (3 genes); cytokines (12 genes); inflammasome (11 genes); Janus kinase/signal transducers and activators of transcription (JAK/STAT, 10 genes); mitogen-activated protein kinase/jun amino-terminal kinases (MAPK/JNK, 3 genes); nuclear factor-kappa beta (NFkB, 18 genes); and NFkB and MAP/JNK (7 genes). After controlling for self-reported and genomic estimates of race and ethnicity, polymorphisms in six genes from the cytokine (2 genes); inflammasome (2 genes); and NFkB (2 genes) pathways were associated with both morning and evening fatigue. Polymorphisms in six genes from the inflammasome (1 gene); JAK/STAT (1 gene); and NFkB (4 genes) pathways were associated with only morning fatigue. Polymorphisms in three genes from the inflammasome (2 genes) and the NFkB (1 gene) pathways were associated with only evening fatigue. Taken together, these findings add to the growing body of evidence that suggests that morning and evening fatigue are distinct symptoms.

Stress and Symptom Burden in Oncology Patients During the COVID-19 Pandemic

“…Previous work from our research team demonstrated that although morning and evening fatigue as well as morning and evening energy are associated with depression, they are distinct symptoms. 74 , 75 , 76 Although cancer-related cognitive impairment occurs in 75% of oncology patients, 34 91.5% of the patients in the stressed class reported clinically meaningful decrements in cognitive function. Finally, although fewer patients in the nonstressed group (54.4%) compared with the stressed group (75.9%) reported pain, both groups reported pain severity scores in the moderate-to-severe range that had a moderate impact on their functional activities.…”

Stability of Symptom Clusters in Patients With Breast Cancer Receiving Chemotherapy

“…The methods for this study are described in detail elsewhere. 5,10–12 In brief, patients were ≥18 years of age; had a diagnosis of breast, GI, gynecological, or lung cancer; had received CTX within the preceding four weeks; were scheduled to receive at least two additional cycles of CTX; were able to read, write, and understand English; and gave written informed consent. Patients were recruited from two Comprehensive Cancer Centers, one Veteran’s Affairs hospital, and four community-based oncology programs.…”

Swiprosin-1 deficiency impairs macrophage immune response of septic mice

“…NF-κB, MAPKs, and JAK/STAT are recognized as the 3 main inflammatory signaling pathways in macrophages, and the activation of these pathways plays a key role in regulating the production of proinflammatory mediators (20). Here, we found that the NF-κB (phosphorylation of IκBα, IKKα/β, and p65) and MAPKs (phosphorylation of p38, JNK, and ERK) pathways were both activated regardless of the presence or absence of swiprosin-1 (Supplemental Figure 6).…”