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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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.