Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and catechol-O-methyl transferase (Val158Met) may be important modulators of opioid efficacy. We assessed joint effects of the OPRM1 and COMT genes in predicting morphine dose for cancer pain relief. We used genotype and clinical data from a pharmacokinetic study of morphine in 207 inpatients treated with stable morphine dose for at least 3 days by Palliative Medicine Specialists. Results showed significant variation in morphine dose requirement by genotype groups: carriers of COMT Val/Val and Val/Met genotype required 63% and 23%, respectively, higher morphine dose compared to carriers of Met/Met genotype (p=0.02). Carriers of OPRM1 GG genotype required 93% higher morphine dose compared to carriers of AA genotypes (p=0.012). When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI=57,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI=100,180). The significant joint effects for the Met/Met and AA genotypes (p<0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose.

Background: Breast cancer diagnosis and treatment can have a profound influence on a woman's physical, psychosocial, and overall well-being. We examined the prevalence of depressive symptoms and its association with health-related quality of life (HRQOL) in women who are survivors of breast cancer. We also assessed if factors, including metastasis, cancer recurrence, diagnosis of new primary cancers, and comorbid conditions, are associated with depressive symptoms. Methods: The Patient Health Questionnaire (PHQ-8) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 were mailed to assess depressive symptoms and HRQOL, respectively, in breast cancer patients who received cancer treatment in a large tertiary cancer center. Results: Two hundred forty patients participated (56% response rate and 6–13 years since treatment). The mean score on the PHQ-8 scale was 4 points (standard deviation [SD] 4.8, median 2.0). Sixteen percent had PHQ-8 score ≥10 and were categorized as depressed. Depression was inversely associated with HRQOL subscales for functioning, financial, and global health and positively associated with symptoms. Logistic regression showed that younger age (odds ratio [OR] age in years 0.92, 95% confidence interval [CI] 0.86- 0.99, p <0.02), rheumatoid arthritis (OR 8.4, 95%CI 1.3-57.4, p <0.03), and years from treatment (OR 0.70, 95% CI 0.46-0.99, p <0.05) were significant correlates of depression. Conclusions: Depression is a significant health concern for breast cancer survivors and is associated with lower HRQOL. The results suggest the need to monitor women with breast cancer for depression and provide resources for treating depression during the survival period.