HLA-Region Genetic Association Analysis of Breast Cancer Patients With and Without Persistent Postsurgical Neuropathic Pain

IF 3.5 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2025-03-14 DOI:10.1002/ejp.70009

L. Mustonen, J. K. Nieminen, S. Koskela, M. Kaunisto, E. Kalso, P. J. Tienari, H. Harno

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引用次数: 0

Abstract

Background

Surgical nerve injuries lead to persistent neuropathic pain (NP) in up to 30% of patients. Among many other factors, polymorphisms in the human leukocyte antigen (HLA) genes have been suggested to contribute to the development of neuropathic pain.

Methods

We performed a genetic association analysis of HLA class I and class II alleles in women who had been operated on for breast cancer. Patients had a surgeon-confirmed perioperative nerve injury and were examined 4–9 years after their surgery. Patients with painful (cases, n = 27) and painless (controls, n = 30) intercostobrachial nerve resection were studied. Cases included patients with definite NP with worst pain intensity in the past week ≥ 4/10 on a numerical rating scale (NRS) and controls had the same nerve injury with no NP or other pains. Whole-genome single nucleotide polymorphism data were produced, and HLA class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQA1, -DQB1 and -DPB1) alleles were determined by imputation.

Results

HLA-DRB1*03:01, DQA1*05:01 and DQB1*02:01 alleles appeared to be associated with painful nerve injury after breast cancer surgery (nominal p = 0.007 for all, carriership OR = 12.0, 95% CI 1.38–104; FDR corrected p > 0.07). These alleles comprise the DR3-DQ2 haplotype, which is part of the ancestral haplotype AH8.1.

Conclusions

Our results provide further support for the role of HLA genetic variation in the development of persistent post-surgical neuropathic pain, which indirectly implies a mechanism involving immunological memory in this process.

Significance Statement

We report a novel association between the HLA-DR3-DQ2 haplotype and the development of persistent neuropathic pain after breast cancer surgery. Our results provide further evidence for the role of HLA polymorphism in persistent neuropathic pain.

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伴有和不伴有持续性术后神经性疼痛的乳腺癌患者hla区域遗传关联分析

手术神经损伤导致高达30%的患者持续神经性疼痛（NP）。在许多其他因素中，人类白细胞抗原（HLA）基因的多态性被认为与神经性疼痛的发生有关。方法对乳腺癌手术患者HLAⅰ类和ⅱ类等位基因进行遗传关联分析。患者经外科医生确认为围手术期神经损伤，术后4-9年复查。对有痛感（27例）和无痛（30例）肋间臂神经切除术患者进行研究。病例包括明确NP患者，过去一周最严重疼痛强度≥4/10 (NRS)，对照组有相同的神经损伤，无NP或其他疼痛。生成全基因组单核苷酸多态性数据，通过代入确定HLA I类（HLA- a、-B、-C）和II类（HLA- drb1、-DQA1、-DQB1和-DPB1）等位基因。结果HLA-DRB1*03:01、DQA1*05:01和DQB1*02:01等位基因与乳腺癌术后疼痛性神经损伤相关(所有等位基因的标称p = 0.007，携带者OR = 12.0, 95% CI 1.38 ~ 104；罗斯福更正了p >； 0.07)。这些等位基因组成DR3-DQ2单倍型，是祖先AH8.1单倍型的一部分。我们的研究结果进一步支持HLA基因变异在术后持续性神经性疼痛发生中的作用，间接暗示免疫记忆参与了这一过程的机制。我们报道了HLA-DR3-DQ2单倍型与乳腺癌手术后持续性神经性疼痛发展之间的新关联。我们的结果为HLA多态性在持续性神经性疼痛中的作用提供了进一步的证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.