Background: Chronic shoulder pain/disability is a well-recognized side effect of treatment for breast cancer, with ∼40% of patients experiencing this, despite receiving pain management. To manage acute and chronic pain, several opioids are commonly prescribed. Pharmacogenomics have implicated genes within the opioid signaling pathway, including ABCB1 and OPRM1, to contribute to an individual's variable response to opioids. Aim: To evaluate ABCB1 (rs1045642 G>A, rs1128503 G>A) and OPRM1 (rs1799971 A>G, rs540825 T>A) single-nucleotide polymorphisms (SNPs) in chronic shoulder pain/disability in BCS. Materials & methods: TaqManTM assays were used to genotype ABCB1 and OPRM1 SNPs within the BCS (N = 252) cohort. The Shoulder Pain and Disability Index was used to evaluate pain and disability features associated with shoulder pathologies. Participants end scores for each feature (pain, disability and combined [pain and disability]) were categorized into no-low (>30%) and moderate-high (≥30%) scores. Statistical analysis was applied, and significance was accepted at p < 0.05. Results: Of participants, 27.0, 19.0 and 22.0% reported moderate-high pain, disability and combined (pain and disability) scores, respectively. ABCB1:rs1045642-(A/A) genotype was significantly associated with disability (p = 0.028: no-low [14.9%] vs mod-high [4.3%]) and combined (pain and disability) (p = 0.011: no-low [15.9%] vs mod-high [5.7%]). The ABCB1:rs1045642-(A) allele was significantly associated with disability (p = 0.015: no-low [37.9%] vs mod-high [23.9%]) and combined (pain and disability) (p = 0.003: no-low [38.5%] vs mod-high [23.6%]). The inferred ABCB1 (rs1045642 G>A - rs1128503 G>A): A-G (p = 0.029; odds ratio [OR]: 0.0; 95% CI: 0.0-0.0) and the OPRM1 (rs1799971 A>G - rs540825 T>A): G-T (p = 0.019; OR: 0.33; 95% CI: 0.14-0.75) haplotypes were associated with disability and pain, respectively. Gene-gene interactions showed the ABCB1 (rs1045642 G>A) - OPRM1 (rs540825 T>A) combinations, (A-T) (p = 0.019; OR: 0.62; 95% CI: 0.33-1.16) and (G-A) (p = 0.021; OR: 1.57; 95% CI: 0.30-3.10) were associated with disability. Conclusion: The study implicated ABCB1 with shoulder pain and disability; and haplotype analyses identified specific genetic intervals within ABCB1 and OPRM1 to associate with chronic shoulder pain and disability. Evidence suggests that potentially gene-gene interactions between ABCB1 and OPRM1 contribute to chronic shoulder pain and disability experienced in this SA cohort.
Keywords: P-glycoprotein; South African breast cancer survivors; genetic association study; gene–gene interactions; mu-opioid receptor.