Gene Polymorphisms of OPRM1 A118G and ABCB1 C3435T May Influence Opioid Requirements in Chinese Patients with Cancer Pain

Abstract

Backgrounds: Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute tointer-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidenceof adverse effects in patients with chronic pain. This study aimed to investigate the association of both twopolymorphisms with opioid requirements in Chinese patients with cancer pain. <br/><b>Methods</b>: The genotypes ofrs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methodsrespectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allelegroups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship ofallele number with opioid response was performed with a trend Jonckheere-Terpstra test. <br/><b>Results</b>: In the 112subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AAcarriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses(P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surfacearea-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). <br/><b>Conclusions</b>: The OPRM1 A118G singlenucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirementsin Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.