Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids

Eivor A. Laugsand; Torill Fladvad; Frank Skorpen; Marco Maltoni; Stein Kaasa; Peter Fayers; Pål Klepstad

doi:10.1016/j.ejca.2011.04.014

Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids

Eivor A. Laugsand^* (Corresponding Author), Torill Fladvad, Frank Skorpen, Marco Maltoni, Stein Kaasa, Peter Fayers, Pål Klepstad

^*Corresponding author for this work

Applied Health Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	1682-1691
Number of pages	10
Journal	European Journal of Cancer
Volume	47
Issue number	11
Early online date	12 May 2011
DOIs	https://doi.org/10.1016/j.ejca.2011.04.014
Publication status	Published - Jul 2011

Bibliographical note

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

Keywords

Adverse effects
Cancer
Emesis
Nausea
Opioid
Palliative care
Single nucleotide polymorphism
Vomiting

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

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title = "Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids",

abstract = "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.",

keywords = "Adverse effects, Cancer, Emesis, Nausea, Opioid, Palliative care, Single nucleotide polymorphism, Vomiting",

author = "Laugsand, {Eivor A.} and Torill Fladvad and Frank Skorpen and Marco Maltoni and Stein Kaasa and Peter Fayers and P{\aa}l Klepstad",

note = "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{\textquoteright}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",

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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

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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.

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KW - Emesis

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KW - Opioid

KW - Palliative care

KW - Single nucleotide polymorphism

KW - Vomiting

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Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids

Abstract

Bibliographical note

Keywords

UN SDGs

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