A Preliminary Prospective Study on the Association of Polymorphisms in BDNF, ARRB2 and KCNJ6 and Response to Fentanyl for Pain Management in Advanced Cancer

Abstract

Introduction: Pain is common in cancer patients, particularly in the advanced stage of the disease with more than 70% prevalence. Despite research regarding cancer pain management, clinicians’ ability to predict and manage patient pain remains a significant challenge. Patients and Methods: This sub-study of a prospective, open label, dose individualization study, investigated how selected single nucleotide polymorphisms (SNPs) in the KCNJ6, ARRB2, and BDNF genes may affect fentanyl dose requirements and response. Fifty-six adult inpatients or outpatients of oncology and pallateive care services who met the eligibility criteria were recruited Administration of transdermal fentanyl was monitored, and participant characteristics (age, height, weight, type of cancer, liver and renal function, fentanyl dose) and pain scores (numerical rating scale) recorded. SNP genotyping was conducted using pyrosequencing (KCNJ6 and BDNF) and TaqMan assays (ARRB2). Statistical analysis included patient characteristics, observed and expected genotype frequencies, genotype and fentanyl dose/pain score, along with categories of low (≤3.0/10) or high (>3.0/10) pain scores and low (≤50 mcg/hr) or high fentanyl doses (>50 mcg/hr). Results: The median fentanyl dose administered was 50 mcg/hr, with a range of 12 to 300 mcg/hr, with the mean pain score 3.0/10.0 (SD:2.3). No association was found between patient characteristics, fentanyl dose, and pain score (P-values >0.05) in the European and Asian population. No association was found for KCNJ6 (rs2070995), ARRB2 (rs34230287, rs3786047, rs1045280, rs2036657), and BDNF (rs7934165, rs10835210, rs1491850) in relation to dose and pain score. Conclusion: These results may show no association between the SNPs examined in KCNJ6, ARRB2, and BDNF with fentanyl dose or response in the population of the study, as this was the case for the subgroups of the population we were able to divide individuals in based on allele groups. This evidence may enhance existing studies, driving the ongoing advancement and refinement of gene-drug dosing guidelines.