Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
J Pain Symptom Manage. 2021 Sep;62(3):e192-e199. doi: 10.1016/j.jpainsymman.2021.03.002. Epub 2021 Mar 12.
Insomnia is a common problem affecting cancer survivors. While effective nonpharmacological treatments are available, it is unknown whether individual genetic characteristics influence treatment response.
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.
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.
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.
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.
失眠是影响癌症幸存者的常见问题。虽然有有效的非药物治疗方法，但尚不清楚个体遗传特征是否会影响治疗反应。
我们在一项针对认知行为疗法治疗失眠症（CBT-I）与针灸治疗的随机试验中，对 11 种遗传变异与失眠症治疗反应的相关性进行了探索性分析，该试验纳入了一组异质的癌症幸存者。
我们成功对 136 名参与者进行了 11 种遗传变异的基因分型。成功的治疗反应定义为从基线到第 8 周时，失眠严重程度指数评分至少降低 8 分。我们使用 Fisher 精确检验评估了每种治疗组中基因型与治疗成功之间的关联，每个治疗组的α水平为 0.05，未调整和 Holm-Bonferroni 调整后的 P 值。
我们发现与 GG 携带者相比，COMT rs4680-A 等位基因的更多携带者对针灸有反应（63.6%对 27.8%，P=0.013）。与 TT 或 CT 携带者相比，NFKB2 rs1056890 CC 基因型的更多携带者对针灸也有反应（72.2%对 38.9%，P=0.009）。在经过多次检验调整后，未发现任何基因变异与 CBT-I 反应之间存在显著差异。
在癌症幸存者中，COMT 和 NFKB2 基因中的特定变异可能与对针灸的反应相关，但与 CBT-I 无关。确认这些初步结果将有助于为癌症幸存者提供精确的失眠症管理。
