TY - JOUR
T1 - Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids
AU - Laugsand, Eivor A.
AU - Fladvad, Torill
AU - Skorpen, Frank
AU - Maltoni, Marco
AU - Kaasa, Stein
AU - Fayers, Peter
AU - Klepstad, Pål
N1 - Acknowledgements
The authors are grateful to all the researchers involved in The European Pharmacogenetic Opioid Study (EPOS).
This study was supported by grants from the European Palliative Care Research Collaborative (EPCRC), the European Commission’s Sixth Framework Programme, the Norwegian University of Science and Technology and the Research Council
of Norway. The funding sources were not involved in study design, in collection, analysis or interpretation of data, in writing of the report or in the decision to submit the paper for publication
PY - 2011/7
Y1 - 2011/7
N2 - Background: This study investigates whether demographical, disease-related and genetic factors contribute to inter-individual differences in nausea and vomiting among patients receiving opioids for cancer pain. Methods: Cancer patients receiving opioids were included from 17 centres in 11 European countries. Intensities of nausea and vomiting were reported by 1579 patients on four-point categorical scales. In stratified regression models including demographical and disease-related factors as covariates, 96 single nucleotide polymorphisms (SNPs) in 16 candidate genes related to opioid- or nausea/vomiting signalling pathways (ABCB1, OPRM1, OPRK1, ARRB2, STAT6, COMT, CHRM3, CHRM5, HRH1, DRD2, DRD3, TACR1, HTR3A, HTR3B, HTR3C, CNR1) were analysed for association with nausea and vomiting. Findings: Age, body mass index, Karnofsky Performance Status, gender, use of antiemetics, type of opioid, type of cancer and eight SNPs were associated with the inter-individual differences in nausea and vomiting among cancer patients treated with opioids (p < 0.01). The SNPs were rs1176744, rs3782025 and rs1672717 in HTR3B; rs165722, rs4680 and rs4633 in COMT; rs10802789 and rs685550 in CHRM3. Only the SNP rs1672717 in HTR3B passed the Benjamini-Hochberg criterion for a 10% false discovery rate. Interpretation: Clinical characteristics and SNPs within the HTR3B, COMT and CHRM3 genes may be associated with the variability in nausea and vomiting among cancer patients receiving opioids. This knowledge may help to identify patients at particular risk for nausea and vomiting during treatment with opioids for cancer pain.
AB - Background: This study investigates whether demographical, disease-related and genetic factors contribute to inter-individual differences in nausea and vomiting among patients receiving opioids for cancer pain. Methods: Cancer patients receiving opioids were included from 17 centres in 11 European countries. Intensities of nausea and vomiting were reported by 1579 patients on four-point categorical scales. In stratified regression models including demographical and disease-related factors as covariates, 96 single nucleotide polymorphisms (SNPs) in 16 candidate genes related to opioid- or nausea/vomiting signalling pathways (ABCB1, OPRM1, OPRK1, ARRB2, STAT6, COMT, CHRM3, CHRM5, HRH1, DRD2, DRD3, TACR1, HTR3A, HTR3B, HTR3C, CNR1) were analysed for association with nausea and vomiting. Findings: Age, body mass index, Karnofsky Performance Status, gender, use of antiemetics, type of opioid, type of cancer and eight SNPs were associated with the inter-individual differences in nausea and vomiting among cancer patients treated with opioids (p < 0.01). The SNPs were rs1176744, rs3782025 and rs1672717 in HTR3B; rs165722, rs4680 and rs4633 in COMT; rs10802789 and rs685550 in CHRM3. Only the SNP rs1672717 in HTR3B passed the Benjamini-Hochberg criterion for a 10% false discovery rate. Interpretation: Clinical characteristics and SNPs within the HTR3B, COMT and CHRM3 genes may be associated with the variability in nausea and vomiting among cancer patients receiving opioids. This knowledge may help to identify patients at particular risk for nausea and vomiting during treatment with opioids for cancer pain.
KW - Adverse effects
KW - Cancer
KW - Emesis
KW - Nausea
KW - Opioid
KW - Palliative care
KW - Single nucleotide polymorphism
KW - Vomiting
UR - http://www.scopus.com/inward/record.url?scp=79959970080&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2011.04.014
DO - 10.1016/j.ejca.2011.04.014
M3 - Article
C2 - 21570824
AN - SCOPUS:79959970080
VL - 47
SP - 1682
EP - 1691
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 11
ER -
