Polymorphisms in Cytokine Genes Are Associated With Higher Levels of Fatigue and Lower Levels of Energy in Women After Breast Cancer Surgery

Abstract

Context Little is known about the phenotypic and molecular characteristics associated with changes over time in fatigue and lack of energy in patients with breast cancer. Objectives To identify subgroups (i.e., latent classes) of women with distinct fatigue and energy trajectories; evaluate for differences in phenotypic characteristics between the latent classes for fatigue and energy; and evaluate for associations between polymorphisms in genes for pro- and anti-inflammatory cytokines, their receptors, and their transcriptional regulators and latent class membership. Methods Patients were enrolled prior to and followed for six months after breast cancer surgery. Latent class analyses were done to identify subgroups of patients with distinct fatigue and energy trajectories. Candidate gene analyses were done to identify cytokine genes associated with these two symptoms. Results For both fatigue and lack of energy, two distinct latent classes were identified. Phenotypic characteristics associated with the higher fatigue class were: younger age, higher education, lower KPS score, higher comorbidity, higher number of lymph nodes removed, and receipt of chemotherapy (CTX). Polymorphisms in interleukin (IL) 1 beta and IL10 were associated with membership in the higher fatigue class. Phenotypic characteristics associated with the lower energy class included: a lower KPS score and a higher comorbidity score. A polymorphism in IL1R1 was associated with membership in the lower energy class. Conclusion Within each latent class, the severity of fatigue and decrements in energy were relatively stable over the first six months following breast cancer surgery. Distinct phenotypic characteristics and genetic polymorphisms were associated with membership in the higher fatigue and lower energy classes.

Distinct evening fatigue profiles in oncology outpatients receiving chemotherapy

“…Only three studies used LPA to identify groups of oncology patients undergoing CTX with distinct fatigue profiles. [12,19,20] In the two studies that used average fatigue scores,[19,20] Higher and Lower Fatigue classes were identified. In both studies, patients in the Higher Fatigue class were significantly younger and reported lower levels of physical activity.…”

Genetic polymorphisms associated with common symptoms experienced by breast cancer patients

“…Furthermore, patients heterozygous or homozygous for IL1R1 (rs2110726) rare variants had decreased odds of belonging to the "lower energy" group. To this point, the results of the Genetic polymorphisms associated with common symptoms experienced by breast cancer patients association between IL1B (rs16944) and the development of fatigue remain contradictory where a study [54] reported increased while the other [59] reported decreased likelihood of belonging to the fatigued group in patients carrying the rare variant allele while two other studies reported no significant association [60,61].…”

“…A number of Single Nucleotide Polymorphisms (SNPs) in proinflammatory cytokines have been reported to be linked with breast cancer susceptibility and prognosis [44][45][46][47][48] as well as the development of treatment-related adverse effects [49,50]. Some evidences have emerged from recent literatures that the energy level in an individual may be considered as a distinct but related symptom to fatigue [51][52][53][54]. Therefore, owing to the relationship between fatigue and energy level, it is hypothesized that a significant number of cytokines and neurotransmitters [55][56][57][58] could play a vital role in the development of these related symptoms.…”

“…A more comprehensive study examining the impact of genetic variation in cytokines and their receptors on fatigue and lack of energy was recently conducted in breast cancer patients before and after breast cancer surgeries [54]. It was observed that patients carrying the homozygous rare variants of IL1B (rs16944) and IL10 (rs3024496) had increased and decreased odds of belonging to the higher fatigue class respectively.…”

Primer in Genetics and Genomics, Article 5—Further Defining the Concepts of Genotype and Phenotype and Exploring Genotype–Phenotype Associations

“…Researchers recently found that in patients followed for 6 months postsurgery for breast cancer, those with the IL1B SNP rs16944 (the number following “rs” is the reference sequence number identifying the specific SNP) with two A alleles (genotype AA) had a 2.98-fold higher risk of belonging to the “higher fatigue” class in their analysis. The phenotypic characteristics of this class included younger age, lower Karnofsky Performance Status score, higher self-administered Comorbidity Questionnaire score, higher fatigue score at study enrollment and higher number of lymph nodes removed (Kober, Smoot, et al, 2016). …”