LAUSR

BACKGROUND Current understanding of genetic factors associated with pain severity, and improvement of pain with opioids in advanced cancer patients (AC) is inadequate for delivery of personalized pain therapy(PPT). Therefore, the aim of this study was to determine the genetic factors associated with pain severity, daily opioid dose, and pain response in AC patients receiving supportive care. METHODS In this prospective study, AC patients were eligible if they had cancer pain ≥4/10 on Edmonton Symptom Assessment Scale (ESAS) - Pain Item and needed opioid rotation for pain control by specialist at the outpatient supportive care center. Pain phenotype was assessed using logistic regression models and SKATO (Gene-block) analysis. RESULTS 174/178 (98%) patient samples were analyzed. After adjustment for demographic and clinical variables, pain severity was negatively associated with intron variant alleles in OPRM1 rs9322446, P = 0.02; rs2270459, P=0.038; rs62052210, P= 0.038. Opioid daily dose was positively associated NFKBIA rs2233419 P=0.008, rs2233417 P=0.007, rs3138054 P=0.008, rs1050851, P= 0.015;ORPM1 rs9479759, P= 0.046, rs2003185, P= 0.047, rs636433, P= 0.044; COMT (rs9306234, P= 0.014, rs165728, P= 0.014, rs2020917, P= 0.036, rs165728, P= 0.034); ARRB2 (rs1045280, P= 0.045); and pain response to opioids was negatively associated OPRM1 rs1319339 p=0.024, rs34427887 P=0.048, and COMT rs4646316 P=0.03, rs35478083 P=0.028 respectively. SKATO analysis showed association between pain severity and CXCL8 (P=0.0056), and STAT6 (P=0.0297) genes respectively, and pain response with IL-6 (P=0.00499). CONCLUSIONS This study identified that SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6,and ARRB2 genes were associated with pain severity, opioid daily dose, and pain response in AC receiving supportive care. Additional studies are needed to validate our findings for PPT. KEY MESSAGE This study shows unique SNPs of OPRM1, COMT, NFKBIA, CXCL8, IL-6, STAT6, and ARRB2 genes were associated with cancer pain severity, and pain response after supportive care consultation in advanced cancer patients. Additional studies are needed to validate our findings for personalized pain therapy.