Tai chi, cellular inflammation, and transcriptome dynamics in breast cancer survivors with insomnia: a randomized controlled trial.
BACKGROUND
Mind-body therapies such as Tai Chi are widely used by breast cancer survivors, yet effects on inflammation are not known. This study hypothesized that Tai Chi Chih (TCC) would reduce systemic, cellular, and genomic markers of inflammation as compared with cognitive behavioral therapy for insomnia (CBT-I).


METHODS
In this randomized trial for the treatment of insomnia, 90 breast cancer survivors with insomnia were assigned to TCC or CBT-I for 2-hour sessions weekly for 3 months. At baseline and postintervention, blood samples were obtained for measurement of C-reactive protein and toll-like receptor-4-activated monocyte production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF), with a random subsample (n = 48) analyzed by genome-wide transcriptional profiling.


RESULTS
Levels of C-reactive protein did not change in the TCC and CBT-I groups. Levels of toll-like receptor-4-activated monocyte production of IL-6 and TNF combined showed an overall reduction in TCC versus CBT-I (P < .02), with similar effects for IL-6 (P = .07) and TNF (P < .05) alone. For genome-wide transcriptional profiling of circulating peripheral blood mononuclear cells, expression of genes encoding proinflammatory mediators showed an overall reduction in TCC versus CBT-I (P = .001). TELiS promoter-based bioinformatics analyses implicated a reduction of activity of the proinflammatory transcription factor, nuclear factor-κB, in structuring these differences.


CONCLUSIONS
Among breast cancer survivors with insomnia, 3 months of TCC reduced cellular inflammatory responses, and reduced expression of genes encoding proinflammatory mediators. Given the link between inflammation and cancer, these findings provide an evidence-based molecular framework to understand the potential salutary effects of TCC on cancer survivorship.
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB). mirwin1@ucla.edu.
Michael R
MR
Irwin
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Richard
R
Olmstead
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Elizabeth C
EC
Breen
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Tuff
T
Witarama
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Carmen
C
Carrillo
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Nina
N
Sadeghi
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Jesusa M G
JM
Arevalo
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Jeffrey
J
Ma
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Perry
P
Nicassio
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Patricia A
PA
Ganz
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Julienne E
JE
Bower
Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, Los Angeles, CA (MRI, RO, ECB, TW, CC, NS, JMGA, JM, PN, JEB, SC); Department of Psychiatry and Biobehavioral Sciences (MRI, RO, ECB, JMGA, JM, PN, JEB, SC), and Department of Medicine (JMGA, PAG, SC), UCLA David Geffen School of Medicine, Los Angeles, CA; Division of Health Policy and Management, UCLA Fielding School of Public Health, Los Angeles, CA (PAG); Division of Cancer Prevention and Control Research, UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA (MRI, PAG, JEB, SC); Department of Psychology, UCLA, Los Angeles, CA (MRI, JEB).
Steve
S
Cole
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000150:complications*; D002097:C-Reactive Protein / Q000378:metabolism; D002478:Cells, Cultured; D015928:Cognitive Behavioral Therapy; D019295:Computational Biology; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000097:blood / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000209:etiology / Q000628:therapy*; D017741:Survivors; D026302:Tai Ji; D051197:Toll-Like Receptor 4 / Q000008:administration & dosage; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein