Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study.
Breast cancer
Cancer-related fatigue
Cytokine gene polymorphism
Post-cancer fatigue
Symptom domain
Journal
Brain, behavior, & immunity - health
ISSN: 2666-3546
Titre abrégé: Brain Behav Immun Health
Pays: United States
ID NLM: 101759062
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
29
10
2020
revised:
04
12
2020
accepted:
06
12
2020
entrez:
30
9
2021
pubmed:
1
10
2021
medline:
1
10
2021
Statut:
epublish
Résumé
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. 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). 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. Genetic factors contribute to the severity and duration of common symptom domains after cancer therapy.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Genetic factors contribute to the severity and duration of common symptom domains after cancer therapy.
Identifiants
pubmed: 34589724
doi: 10.1016/j.bbih.2020.100189
pii: S2666-3546(20)30154-X
pmc: PMC8474532
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100189Informations de copyright
© 2020 The Authors.
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