Genetic and Clinical Factors Associated with Opioid Response in Chinese Han Patients with Cancer Pain: An Exploratory Cross-Sectional Study.

Abstract

IntroductionStudies have shown that genetic variation and environmental factors are associated with individual differences in therapeutic efficacy and side effects of opioids. However, the focus of these studies has been on a single factor of single-nucleotide polymorphisms (SNPs) or haplotypes, for which results have rarely been validated. For complex traits, such as cancer pain and opioid response, interactions between multiple genetic variation and environmental factors need to be considered to explain the opioid individual differences.MethodsWe conducted an exploratory two-stage cross-sectional study with 1027 Chinese patients who were taking strong opioid medications for their cancer pain, and genotyped 110 SNPs to explore the association of SNPs, haplotypes, gene–gene and gene–environment interactions with opioid dose, pain relief, and opioid-induced constipation.ResultsDue to the failure to meet Benjamini–Hochberg criteria in the discovery stage or to be validated in replication stage, no association was found between SNPs, haplotypes, paired SNP–SNP interactions or multi-dimensional gene–gene interactions and opioid response. However, for gene–environment interactions, optimal models have been constructed in all phenotypes of opioid response.ConclusionsThis study reveals for the first time that construction of multidimensional gene–environment interactions enables better interpretations of the effect of genetic variation and environmental factors on the opioid response in patients with cancer pain.Trial registrationChictr.org.cn, identifier, ChiCTR2000033576.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40122-022-00353-5.