9129 Background: Morphine sulfate is the most widely used opioid in oncologic pain. There is a high variability in response between individuals. The objectives are to correlate the variability in response (R) and tolerability with polymorphisms within OPRM1, β-arrestin 2, STAT6 and COMT gene sequences. Methods: DNA from 44 oncologic patients (pts) with an EVA score > 6 was prospectively analyzed using allelic discrimination techniques and automatic sequencing. Pts (never treated with opioids) received morphine sulfate 10 mg per day. Pain was assessed by EVA score and toxicity was evaluated according to the most common opioid side effects. Symptomatology was reassessed after 72 hours. Chi-squared and Fisher’s tests where used to analyze data. Results: 17 pts (38.6%) responded with an EVA < 3. 6 pts (13.6%) did not experience toxicity, 36 pts (81.8%) had mild side effects and 2 pts (4.5%) had severe side effects. There was no relation between R rate (RR) and tolerance. 76.5% of pts responding to treatment had a CC/CT β-arrestin 2 genotype and this was associated with a better RR (CC/CT R = 46.4% vs. TT R = 25% p = 0.16). The 2 pts having severe side effects belonged to CC/CT group. COMT genotypes AA/GA were associated with a higher RR (83.3%pts) and better tolerance (100% pts with no toxicities). OPRM1 genotype GG was associated with both treatment failure (0% responded) and worse tolerance (any toxicity = 100%; severe side effects = 33%). Only 2,4% pts in the AA/GA genotype experienced some toxicity (p = 0.041). Although STAT6 genotypes were not associated with RR, tolerance was better in those pts with an AA or GA genotype with 97.5% pts showing either mild or no side effects (p = 0.007). Conclusions: Common variants in β-arrestin 2, COMT, OPRM1 and STAT6 genes have shown to predict for opioid-associated response and side effects in oncologic patients. Further studies are needed to assess factors determining the variability in response and tolerance to opioid treatment.