Timothy J Genovese1, Philip Gehrman2, MingXiao Yang3, Yuelin Li4, Sheila N Garland5, Irene Orlow6, Jun J Mao7. 1. Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Warren Alpert Medical School of Brown University, Providence, RI, USA. 2. Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA. 3. Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Departments of Psychology and Oncology, Memorial University of Newfoundland, St. John's, Newfoundland, Canada. 6. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 7. Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: maoj@mskcc.org.
Abstract
CONTEXT: Insomnia is a common problem affecting cancer survivors. While effective nonpharmacological treatments are available, it is unknown whether individual genetic characteristics influence treatment response. OBJECTIVES: We conducted an exploratory analysis of genetic associations with insomnia treatment response in a randomized trial of cognitive behavioral therapy for insomnia (CBT-I) vs. acupuncture in a heterogeneous group of cancer survivors. METHODS: We successfully genotyped 136 participants for 11 genetic variants. Successful treatment response was defined as a reduction in Insomnia Severity Index score of at least eight points from baseline to week 8. We used Fisher exact tests to evaluate associations between genotype and treatment success for each treatment arm, for an alpha level of 0.05 with unadjusted and Holm-Bonferroni-adjusted P-values. RESULTS: We found that more carriers of COMT rs4680-A alleles responded to acupuncture compared to the GG carriers (63.6% vs. 27.8%, P = 0.013). More carriers of the NFKB2 rs1056890 CC genotype also responded to acupuncture compared to TT or CT carriers (72.2% vs. 38.9%, P = 0.009). There were no significant differences found between any of the tested gene variants and CBT-I response. None of the results remained statistically significant after adjustment for multiple testing. CONCLUSION: In cancer survivors, specific variants in the COMT and NFKB2 genes are potentially associated with response to acupuncture but not to CBT-I. Confirming these preliminary results will help inform precision insomnia management for cancer survivors.
CONTEXT: Insomnia is a common problem affecting cancer survivors. While effective nonpharmacological treatments are available, it is unknown whether individual genetic characteristics influence treatment response. OBJECTIVES: We conducted an exploratory analysis of genetic associations with insomnia treatment response in a randomized trial of cognitive behavioral therapy for insomnia (CBT-I) vs. acupuncture in a heterogeneous group of cancer survivors. METHODS: We successfully genotyped 136 participants for 11 genetic variants. Successful treatment response was defined as a reduction in Insomnia Severity Index score of at least eight points from baseline to week 8. We used Fisher exact tests to evaluate associations between genotype and treatment success for each treatment arm, for an alpha level of 0.05 with unadjusted and Holm-Bonferroni-adjusted P-values. RESULTS: We found that more carriers of COMT rs4680-A alleles responded to acupuncture compared to the GG carriers (63.6% vs. 27.8%, P = 0.013). More carriers of the NFKB2 rs1056890 CC genotype also responded to acupuncture compared to TT or CT carriers (72.2% vs. 38.9%, P = 0.009). There were no significant differences found between any of the tested gene variants and CBT-I response. None of the results remained statistically significant after adjustment for multiple testing. CONCLUSION: In cancer survivors, specific variants in the COMT and NFKB2 genes are potentially associated with response to acupuncture but not to CBT-I. Confirming these preliminary results will help inform precision insomnia management for cancer survivors.
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