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Opioid response varies widely among cancer patients, posing a challenge for effective pain management. A recent genome-wide association study (GWAS) by Nishizawa et al. (2022) examined 428 Japanese cancer pain patients and identified significant genetic loci associated with opioid analgesic requirements. Two intronic single-nucleotide polymorphisms (SNPs), rs1283671 and rs1283720, showed genome-wide significance ( p < 5 × 10−8) for association with higher daily opioid dose needed for pain control. These variants are located in the angiopoietin-1 (ANGPT1) gene, which encodes an angiogenic factor involved in vascular stability and inflammation. The minor alleles were associated with lower opioid sensitivity (i.e., requiring higher opioid doses). Gene-level analysis also highlighted the SLC2A14 gene (encoding the GLUT14 glucose transporter) as significantly associated with opioid dose in cancer pain. While SLC2A14’s role in opioid pharmacodynamics is unclear, its identification alongside ANGPT1 suggests novel biological pathways (angiogenesis and metabolism) influencing analgesic efficacy. Notably, these SNPs in ANGPT1 and SLC2A14 could serve as predictive markers for opioid efficacy in cancer pain treatment, paving the way for personalized analgesic regimens.In addition, our GWAS (2014) in patients who underwent cosmetic orthognathic surgery uncovered a potent locus on chromosome 2 (2q33–34) that affects postoperative opioid sensitivity. The lead SNP, rs2952768, was associated with increased postoperative opioid analgesic requirements (C allele carriers needed higher opioid doses). Functional analyses revealed that the rs2952768 C/C genotype correlates with elevated expression of the neighboring CREB1 gene, which encodes a key transcription factor involved in neural plasticity. This 2q33 locus was reported as one of the most influential genetic factors for human opioid sensitivity to date.The convergence of evidence from cancer pain and postoperative pain studies suggests that variants in genes related to angiogenesis (ANGPT1), metabolism (SLC2A14), and neural regulation (CREB1) can significantly impact opioid efficacy and tolerability. These insights provide a foundation for improving cancer pain management through pharmacogenomics, allowing more precise and individualized opioid therapy.