RT Journal Article
SR Electronic
T1 Lack of association between genetic variability and multiple pain-related outcomes in a large cohort of patients with advanced cancer: the European Pharmacogenetic Opioid Study (EPOS)
JF BMJ Supportive & Palliative Care
JO BMJ Support Palliat Care
FD British Medical Journal Publishing Group
SP 351
OP 355
DO 10.1136/bmjspcare-2012-000212
VO 2
IS 4
A1 Torill Fladvad
A1 Peter Fayers
A1 Frank Skorpen
A1 Stein Kaasa
A1 Pål Klepstad
YR 2012
UL http://spcare.bmj.com/content/2/4/351.abstract
AB Objective This study examined whether the choice of pain-related outcome to represent opioid efficacy influenced findings in a genetic association study. Data from the European Pharmacogenetic Opioid Study, which used opioid dose as the outcome, were analysed in respect of six alternative outcomes: average pain intensity, pain right now, worst pain intensity, pain at its least, pain relief and pain interference. Design Cancer pain patients using an opioid for moderate or severe pain were included. The pain outcomes were obtained using the Brief Pain Inventory. Genetic variation was analysed for 112 single nucleotide polymorphisms (SNPs) in 25 candidate genes relevant for opioid efficacy. The patients were randomly divided into a development and a validation sample and linear regression was used to compare the equality of means in the six outcomes. The influence of non-genetic factors was controlled for, the regression analyses were stratified by country, and the results were corrected for multiple testing. Results 2201 cancer pain patients were included. Their mean age was 62.4 years and mean average pain was 3.5. None of the examined SNPs exceeded p values corrected for multiple testing for any of the outcomes. Conclusions None of the outcomes were associated with variation in the selected SNPs, as previously shown for opioid dose. Thus, we observed that findings related to associations between genetic variability and opioid efficacy were consistent for several alternative outcomes.