Photo Credit: Claudio Ventrella

The following is a summary of “A genome-wide association study of European advanced cancer patients treated with opioids identifies regulatory variants on chromosome 20 associated with pain intensity,” published in the December 2024 issue of Pain by Minnai et al. 

Researchers conducted a retrospective study to analyze the role of genetics in predicting opioid response in patients with cancer pain using a genome-wide association study (GWAS).   

They genotyped 2,057 European patients with advanced cancer who were treated with morphine, buprenorphine, fentanyl, or oxycodone. A whole-genome regression model was performed using REGENIE software to analyze the relationship between genotypes and opioid response, defined by a numerical score reflecting patient pain intensity.  

The results showed 5 non-coding variants on chromosome 20 were identified in the GWAS with a P -value <5.0 × 10^-8. For all variants, the minor allele was linked to lower pain intensity. These variants were intronic to the PCMTD2 gene and located 200 kbp downstream of OPRL1, the opioid-related nociceptin receptor 1. According to the eQTLGen database, these variants act as expression quantitative trait loci, primarily influencing the expression of PCMTD2 and also affecting OPRL1. Variants in the chromosomal region were recently found to be associated with pain intensity in a separate GWAS involving individuals with various chronic pain conditions.  

Investigators concluded the genetic factors influenced the opioid response in patients with advanced cancer, emphasizing the need for further functional studies to elucidate the underlying mechanisms and inform personalized pain management strategies for improved patient outcomes. 

Source: onlinelibrary.wiley.com/doi/full/10.1002/ejp.4764