Genetics of Chronic Shoulder Pain/Disability in South African Breast Cancer Survivors: Polygenic Contributions by Opioid and Pain Signaling Pathways

Chronic shoulder pain/disability is a significant cause of morbidity among breast cancer survivors, which can persist for several years postsurgery, thus markedly impacting their quality of life. The condition is a multifactorial and polygenic trait. In this overarching context, we report here on the polygenic effects through polymorphisms in opioid signaling and pain pathways, specifically, the (1) ATP-binding cassette subfamily B, member 1 gene-catechol-O-methyltransferase (<i>ABCB1-COMT</i>) and (2) <i>ABCB1</i>-opioid receptor Mu 1 (<i>OPRM1</i>)-<i>COMT</i> genes. Using TaqMan™ assays, we genotyped the polymorphisms in the candidate genes in a sample of South African breast cancer survivors (<i>N</i> = 252) reporting chronic shoulder pain/disability. The Shoulder Pain and Disability Index was used to evaluate pain/disability symptoms, with total scores converted to percentages and participants categorized as no-low (< 30%) or moderate-high (≥ 30%). The <i>ABCB1</i> (rs1128503)-<i>COMT</i> (rs4680) G-A allele combination was significantly associated with increased pain (<i>p </i>= 0.005, odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.12-3.84) and combined (<i>p </i>= 0.008, OR: 1.94, 95% CI: 1.02-3.69) symptoms. Furthermore, the <i>ABCB1</i> (rs1045642)-<i>OPRM1</i> (rs1799971)-<i>COMT</i> (rs4680) G-A-A allele combination was associated with increased pain (<i>p</i> < 0.001, OR: 1.93, 95% CI: 1.01-3.69) and combined (<i>p</i> < 0.001, OR: 1.60, 95% CI: 0.81-3.19) symptoms. Collectively, these findings suggest that chronic shoulder pain/disability in breast cancer survivors in this sample of South African patients is influenced by the combined effects of polymorphisms within the <i>ABCB1</i>-<i>OPRM1</i>-<i>COMT</i> genes. These observations present the potential for further translational research, personalized medicine, and pain management strategies to improve the long-term quality of life in breast cancer patients.