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



The aim of this study was 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.



Patients were enrolled before 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.



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 Karnofsky Performance Status score, higher comorbidity, higher number of lymph nodes removed, and receipt of chemotherapy (CTX). Polymorphisms in interleukin (IL) 1β and IL10 were associated with membership in the higher fatigue class. Phenotypic characteristics associated with the lower energy class included: a lower Karnofsky Performance Status score and a higher comorbidity score. A polymorphism in IL1R1 was associated with membership in the lower energy class.



Within each latent class, the severity of fatigue and decrements in energy were relatively stable over the first six months after breast cancer surgery. Distinct phenotypic characteristics and genetic polymorphisms were associated with membership in the higher fatigue and lower energy classes.
School of Nursing, University of California, San Francisco, California, USA. Electronic address: kord.kober@ucsf.edu.
Kord M
KM
Kober
School of Medicine, University of California, San Francisco, California, USA.
Betty
B
Smoot
School of Nursing, University of California, San Francisco, California, USA.
Steven M
SM
Paul
School of Nursing, University of California, San Francisco, California, USA.
Bruce A
BA
Cooper
School of Medicine, University of California, San Francisco, California, USA.
Jon D
JD
Levine
School of Nursing, University of California, San Francisco, California, USA.
Christine
C
Miaskowski
D000367:Age Factors; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000601:surgery*; D015897:Comorbidity; D016207:Cytokines / Q000235:genetics*; D004522:Educational Status; D005221:Fatigue / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D017567:Karnofsky Performance Status; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011183:Postoperative Complications / Q000453:epidemiology / Q000235:genetics*; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics
D000970:Antineoplastic Agents; D016207:Cytokines; C508590:IL1R1 protein, human; D053573:Receptors, Interleukin-1 Type I
Fatigue; breast cancer; cytokine genes; energy; growth mixture modeling; symptom trajectories
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