From the Departments of Health Outcomes and Behavior (Hoogland, Gonzalez, Smith, Jacobsen, Jim), and Cancer Epidemiology (Park), Moffitt Cancer Center; College of Aging (Small), University of South Florida; Departments of Biostatistics and Bioinformatics (Small, Sutton), and Blood and Marrow Transplantation and Cellular Immunotherapy (Pidala), Moffitt Cancer Center, Tampa, Florida; and Department of Psychology (Bower), University of California-Los Angeles, Los Angeles, California.
Psychosom Med. 2023;85(9):813-819. doi: 10.1097/PSY.0000000000001251. Epub 2023 Sep 6.
Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT).
Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate-adjusted p value of <.05.
The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time ( p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 ( p = 3.0 × 10 -4 ) and rs6311 ( p = 2.0 × 10 -4 ) in HTR2A . Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 ( p = 6.0 × 10 -5 ) and a patient-donor interaction at rs1885884 in HTR2A ( p < 1.0 × 10 -4 ).
Data suggest that variants in genes regulating the serotonergic system ( HTR2A ) and lipid metabolism ( SORL1 ) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients' own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.
抑郁和疲劳是癌症患者常见的症状，与种系遗传变异有关。本研究的目的是在异基因造血细胞移植（HCT）后 1 年内，研究遗传因素与抑郁和疲劳的相关性。
在 HCT 前采集患者及其供者的血液。患者在 HCT 前（T1）、HCT 后 90 天（T2）和 HCT 后 1 年（T3）完成抑郁和疲劳的自我报告量表评估。在定制的 Illumina BeadChip 微阵列上进行基因分型的 384 个遗传变异中，基于质量控制保留了 267 个用于分析。使用回归分析检查患者和供者变异的主效应及其相互作用。将具有调整后的假发现率 p 值 <.05 的显著变异定义为显著变异。
样本包括 59 对患者-供者。抑郁和疲劳的平均水平随时间没有明显变化（p 值均 >.41）。从 T1 到 T2 抑郁的增加与 HTR2A 中的 rs1928040（p = 3.0×10-4）和 rs6311（p = 2.0×10-4）的患者-供者相互作用有关。从 T1 到 T2 疲劳的增加与 SORL1 中的患者 rs689021（p = 6.0×10-5）和 HTR2A 中的患者-供者相互作用 rs1885884 有关（p < 1.0×10-4）。
数据表明，调节 5-羟色胺能系统（HTR2A）和脂质代谢（SORL1）的基因中的变异与异基因 HCT 患者的抑郁和疲劳变化有关，这暗示了患者自身的遗传遗传以及供者的遗传遗传。需要进一步的研究来证实这些发现。
