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肺癌患者 ERCC1 和 ERCC2 基因多态性与生活质量、抑郁和焦虑状态的关联。

Genetic polymorphisms and haplotypes of ERCC1 and ERCC2 associated with quality of life, depression, and anxiety status among patients with lung cancer.

机构信息

Department of Medical Psychology, College of Psychology, Naval Medical University, 800 Xiangyin Rd., Shanghai, 200433, China.

出版信息

BMC Cancer. 2021 Jul 21;21(1):842. doi: 10.1186/s12885-021-08570-5.

Abstract

BACKGROUND

Patients with lung cancer (LC) have a poor quality of life (QoL) and easily suffer from psychological diseases. Previous studies focused less on the relationship between genetic factors and QoL, depression, and anxiety status in LC patients. The current study is intended to explore the relationship between SNPs and haplotypes of ERCC1 and ERCC2 and the QoL, depression and anxiety status of patients with LC.

METHODS

QoL, depression and anxiety status were assessed in 291 LC patients using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30), EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), SDS and SAS. Nine tag SNPs of ERCC1 and ERCC2 were detected using an improved multiplex ligation detection reaction (iMLDR) technique. Haplotype analysis was conducted using the software Haploview 4.2. The association between SNPs or haplotypes and QoL or depression or anxiety in LC patients was analyzed by regression analysis.

RESULTS

ERCC1 rs11615 was associated with emotional functioning (P = 0.027), and ERCC1 rs3212986 was associated with anxiety scores (P = 0.018). ERCC1 rs762562-rs3212986 haplotype was associated with cognitive function (P = 0.029), somatic function (P = 0.014) and dysphagia (OR = 3.32, P = 0.044). Patients with ERCC1 rs3212986-rs11615 AG haplotype had worse cognitive function (adjusted Beta = - 5.42) and somatic function (adjusted Beta = - 6.55) and had severer symptoms of loss of appetite (adjusted OR = 1.67) and dysphagia (adjusted OR = 4.43) (All adjusted P < 0.05). ERCC2 rs13181-rs3916874-rs238416 haplotype was associated with emotional functioning (P = 0.035), pain at other sites (OR 1.88, P = 0.014), chest pain (OR 0.42, P = 0.02), dysphagia (OR 2.82, P = 0.048), and anxiety status (OR 0.23, P = 0.009).

CONCLUSION

After adjustment for environmental factors, SNPs and haplotypes of ERCC1 and ERCC2 were associated with different domains of QoL, depression and anxiety in LC patients.

摘要

背景

肺癌 (LC) 患者生活质量 (QoL) 较差,且易患心理疾病。既往研究较少关注遗传因素与 LC 患者 QoL、抑郁和焦虑状态之间的关系。本研究旨在探讨 ERCC1 和 ERCC2 的单核苷酸多态性 (SNP) 及其单倍型与 LC 患者 QoL、抑郁和焦虑状态之间的关系。

方法

采用欧洲癌症研究与治疗组织 (EORTC) 核心生活质量问卷 (QLQ-C30)、EORTC 肺癌生命质量问卷 13 (QLQ-LC13)、SDS 和 SAS 对 291 例 LC 患者的 QoL、抑郁和焦虑状态进行评估。采用改良多重连接检测反应 (iMLDR) 技术检测 ERCC1 和 ERCC2 的 9 个标签 SNP。采用 Haploview 4.2 软件进行单倍型分析。采用回归分析分析 SNP 或单倍型与 LC 患者 QoL 或抑郁或焦虑之间的关系。

结果

ERCC1 rs11615 与情绪功能相关 (P=0.027),ERCC1 rs3212986 与焦虑评分相关 (P=0.018)。ERCC1 rs762562-rs3212986 单倍型与认知功能 (P=0.029)、躯体功能 (P=0.014) 和吞咽困难相关 (OR=3.32,P=0.044)。携带 ERCC1 rs3212986-rs11615 AG 单倍型的患者认知功能 (调整后的 Beta=-5.42) 和躯体功能 (调整后的 Beta=-6.55) 更差,且食欲不振 (调整后的 OR=1.67) 和吞咽困难 (调整后的 OR=4.43) 的症状更严重 (均为 P<0.05)。ERCC2 rs13181-rs3916874-rs238416 单倍型与情绪功能 (P=0.035)、其他部位疼痛 (OR 1.88,P=0.014)、胸痛 (OR 0.42,P=0.02)、吞咽困难 (OR 2.82,P=0.048) 和焦虑状态 (OR 0.23,P=0.009) 相关。

结论

在调整环境因素后,ERCC1 和 ERCC2 的 SNP 和单倍型与 LC 患者的 QoL、抑郁和焦虑的不同领域相关。

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