遗传对乳腺癌正念减压疗法(MBSR(BC))效果的调节作用认知障碍计划

Jong Y Park, Cecile A Lengacher, Carmen S Rodriguez, Hongdao Meng, Kevin E Kip, Sandra Morgan, Anisha Joshi, Gizem Hueluer, Julia R Wang, Sara Tinsley, Charles Cox, John Kiluk, Kristine A Donovan, Manolete Moscoso, Elizabeth Bornstein, Jean M Lucas, Tamela Fonseca, Mahathi Krothapalli, Lynne S Padgett, Sreenidhi Nidamanur, Estella Hornback, Diya Patel, Ramya Chamkeri, Richard R Reich
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引用次数: 0

摘要

背景:遗传可能会影响乳腺癌幸存者(BCS)所经历的症状,从而调节减压干预措施(包括正念减压(MBSR(BC))计划)对减轻症状严重程度的影响。作为一项大型临床试验的一部分,本研究旨在评估基因变异对MBSR(BC)改善BCS认知功能和症状的调节作用:乳腺癌患者(n = 128)被随机分配到 MBSR(BC)或乳腺癌教育支持计划中。在基线、6周、12周和26周收集了认知功能、心理和身体症状的客观神经心理学和主观测量数据。采用线性混合模型来确定 MBSR(BC) 随时间变化的影响。利用基因组 DNA 对已知与这些症状相关的 20 个基因中的 22 个单核苷酸多态性 (SNP) 进行了调查。这些SNPs作为MBSR(BC)项目效果的调节因子进行了测试:结果表明,MBSR(BC)参与者在认知功能方面的获益明显增加,但获益程度因个人遗传特征而异。研究还调查了效应大小以及类似测量的一致性。在 22 个候选 SNPs 中,COMT 的 rs4680、ANKK1 的 rs1800497 和 DRD2 的 rs6277 在调节 MBSR(BC)对认知结果的影响方面表现出最强、最一致的积极效应:虽然影响很小,但这项转化研究有可能识别出受 MBSR(BC)计划影响最大的 BCS 基因型。这些结果可用于为每位接受化疗或化疗和放疗的乳腺癌幸存者量身定制个性化干预方案:ClinicalTrials.gov, https://www.ClinicalTrials.gov 注册号:NCT02786797。
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The Moderating Role of Genetics on the Effectiveness of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) Program on Cognitive Impairment.

Background: Genetics may influence symptoms experienced by breast cancer survivors (BCS) by moderating the effects of stress-reducing interventions, including the Mindfulness-Based Stress Reduction (MBSR(BC)) program, to reduce symptom severity. As part of a larger clinical trial, the aim of this study was to evaluate genetic variants as moderators of MBSR(BC) on improvements among BCS in cognitive functioning and symptoms.

Methods: BCS (n = 128) were randomized to MBSR(BC) or the Breast Cancer Education Support Program. Objective neuropsychological and subjective measures of cognitive performance, and psychological and physical symptoms were collected at baseline, 6, 12, and 26 weeks. Linear mixed models were implemented to identify MBSR(BC)'s effects over time. A total of 22 single nucleotide polymorphisms (SNPs) from 20 genes known to be related to these symptoms were investigated using genomic DNA. These SNPs were tested as moderators of MBSR(BC) program effects.

Results: Results showed MBSR(BC) participants experienced significantly greater benefits in cognitive functioning, however, the level of benefit varied based on one's genetic profile. Effects sizes, consistency across similar measures were investigated. Among 22 candidate SNPs, rs4680 in COMT, rs1800497 in ANKK1, and rs6277 in DRD2 demonstrated the strongest, most consistent positive effects in moderating MBSR(BC)'s impact on cognitive outcomes.

Conclusions: Although the effects were small, this translational research may potentially identify BCS with genotypes that would be most influenced by the MBSR(BC) program. These results may be used to develop personalized intervention programs tailored to the genetic profile of each breast cancer survivor who received chemotherapy or chemotherapy and radiation.

Trial registration: ClinicalTrials.gov, https://www.ClinicalTrials.gov Registration Number: NCT02786797.

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