Polymorphisms in COMT and OPRM1 Collectively Contribute to Chronic Shoulder Pain and Disability in South African Breast Cancer Survivors’

Abstract

Chronic shoulder pain and disability is a common adverse effect experienced by >40% of breast cancer survivors (BCS). Pain management protocols for acute and chronic pain include the use of opioids and opioid derivatives. Furthermore, pain-modulating genes, such as COMT and OPRM1, have been linked to the aetiology of chronic pain. This study aimed to investigate the association between genetic variants of major pain modulator genes and chronic pain/disability in BCS. Assessment of pain, disability and combined (pain and disability) symptoms were determined using the Shoulder Pain and Disability Index (SPADI). Participants were grouped according to their scores such as no-low (<30%) and moderate-high (≥30%) groups of pain, disability and combined (pain and disability). Genotyping of the COMT rs6269 (A > G), rs4633 (C > T), rs4818 (C > G) and the functional rs4680(G > A) SNPs within the BCS (N = 252) cohort were conducted using TaqMan® SNP assays. Genotype, allele, haplotype, and allele–allele combination frequencies were evaluated. Statistical analysis was applied, with significance accepted at p < 0.05. The COMT rs4680:A/A genotype was significantly associated with moderate-high pain (p = 0.024, OR: 3.23, 95% CI: 1.33–7.81) and combined (pain and disability) (p = 0.015, OR: 3.81, 95% CI: 1.47–9.85). The rs4680:A allele was also significantly associated with moderate-high pain (p = 0.035, OR: 1.58, 95% CI: 1.03–2.43) and combined (pain and disability) (p = 0.017, OR: 1.71, 95% CI: 1.07–2.71). For the inferred COMT (rs6269 A > G-rs4680 G > A) haplotype analyses, the G-G (p = 0.026, OR: 0.67, 95% CI: 0.38–1.18) and A-A (p = 0.007, OR: 2.09, 95% CI: 0.89–4.88) haplotypes were significantly associated with reduced and increased likelihoods of reporting moderate-high pain, respectively. The inferred A-A (p = 0.003, OR: 2.18, 95% CI: 0.92–5.17) haplotype was also significantly associated with combined (pain and disability). Gene–gene interaction analyses further showed allele–allele combinations for COMT (rs4680 G > A)-OPRM1 (rs1799971 A > G) and COMT (rs4680 G > A)-OPRM1(rs540825 T > A) were associated with reporting pain and combined (pain and disability) symptoms, p < 0.05. The findings of this study suggest that COMT and OPRM1 SNPs play a role in the development of chronic shoulder pain/disability in BCS in a unique South African cohort from the Western Cape.