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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 languageEnglish
Pages (from-to)1682-1691
Number of pages10
JournalEuropean Journal of Cancer
Volume47
Issue number11
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Nausea
Opioid Analgesics
Vomiting
Single Nucleotide Polymorphism
Neoplasms
Individuality
Karnofsky Performance Status
Inborn Genetic Diseases
Antiemetics
Genes
Body Mass Index

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids. / Laugsand, Eivor A.; Fladvad, Torill; Skorpen, Frank; Maltoni, Marco; Kaasa, Stein; Fayers, Peter; Klepstad, Pål.

In: European Journal of Cancer, Vol. 47, No. 11, 07.2011, p. 1682-1691.

Research output: Contribution to journalArticle

Laugsand, Eivor A. ; Fladvad, Torill ; Skorpen, Frank ; Maltoni, Marco ; Kaasa, Stein ; Fayers, Peter ; Klepstad, Pål. / Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids. In: European Journal of Cancer. 2011 ; Vol. 47, No. 11. pp. 1682-1691.
@article{29ddfaf8392f4c319acc612b20459b72,
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",
year = "2011",
month = "7",
doi = "10.1016/j.ejca.2011.04.014",
language = "English",
volume = "47",
pages = "1682--1691",
journal = "European Journal of Cancer",
issn = "0959-8049",
publisher = "Elsevier Ltd",
number = "11",

}

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

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

UR - http://www.scopus.com/inward/citedby.url?scp=79959970080&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2011.04.014

DO - 10.1016/j.ejca.2011.04.014

M3 - Article

VL - 47

SP - 1682

EP - 1691

JO - European Journal of Cancer

JF - European Journal of Cancer

SN - 0959-8049

IS - 11

ER -