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. 2020 Dec 8:10:100189.
doi: 10.1016/j.bbih.2020.100189. eCollection 2021 Jan.

Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study

B Cameron  1 , K Webber  2 , H Li  1 , B K Bennett  2 , F Boyle  3 , P de Souza  4 , N Wilcken  5 , J Lynch  6 , M Friedlander  7 , D Goldstein  1   2 , A R Lloyd  1   2
Affiliations

Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study

B Cameron et al. Brain Behav Immun Health. .

Abstract

Background: Cancer-related fatigue, mood disturbances, pain and cognitive disturbance are common after adjuvant cancer therapy, but vary considerably between individuals despite common disease features and treatment exposures. A genetic basis for this variability was explored in a prospective cohort.

Methods: Physical and psychological health of women were assessed prospectively following therapy for early stage breast cancer with self-report questionnaires. Participation in a genetic association sub-study was offered. Indices for the key symptom domains of fatigue, pain, depression, anxiety, and neurocognitive difficulties were empirically derived by principal components analysis from end-treatment questionnaires, and then applied longitudinally. Genetic associations were sought with functional single nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes - tumour necrosis factor (TNF)-α (-308 ​GG), interferon (IFN)-ɣ (+874 ​TA), interleukin (IL)-10 (1082 ​GA and -592 CA), IL-6 (-174 ​GC), IL-1β (-511 ​GA).

Results: Questionnaire data was available for 210 participants, of whom 111 participated in the genetic sub-study. As expected, symptom domain scores generally improved over several months following treatment completion. Tumour and adjuvant treatment related factors were unassociated with either severity or duration of the individual symptom domains, but severity of symptoms at end-treatment was strongly associated with duration for each domain (all p ​< ​0.05). In multivariable analyses, risk genotypes were independently associated with: fatigue with IL-6 -174 ​GG/GC and IL-10 -1082 GG; depression and anxiety with IL-10 -1082 AA; neurocognitive disturbance: TNF-α -308 GG; depression IL-1β (all p ​< ​0.05). The identified SNPs also had cumulative effects in prolonging the time to recovery from the associated symptom domain.

Conclusions: Genetic factors contribute to the severity and duration of common symptom domains after cancer therapy.

Keywords: Breast cancer; Cancer-related fatigue; Cytokine gene polymorphism; Post-cancer fatigue; Symptom domain.

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Figures

Fig. 1
Fig. 1
The FolCan and genetic substudy cohorts.
Fig. 2
Fig. 2
Survival curves for fatigue, depression, and anxiety symptom domains by risk or protective genotypes. (A) Duration of fatigue by protective genotype (IL-6 -174 CC and IL-10 -1082 GG or GA) compared with the risk genotype (IL-6 -174 CG or GG and IL-10 -1082 AA). (B) Duration of depression by protective genotype (IL-1β −511 GG and IL-10 -1082 GG) compared with the risk genotype (IL-1 β −511 AA or AG and IL-10 -1082 AA). (C) Genetic effect of protective genotypes IL-10 -1082 GG or GA on duration of the anxiety symptom domain compared with the risk genotype (IL-10 -1082 AA). N ​= ​94 for all graphs. Solid lines are protective genotypes, dashed lines are risk genotypes. The zero timepoint refers to end-treatment. Kaplan-Meir survival analysis.
See this image and copyright information in PMC

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