Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

Eivor A. Laugsand* (Corresponding Author), Frank Skorpen, Stein Kaasa, Rainer Sabatowski, Florian Strasser, Peter Fayers, Pål Klepstad

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

OBJECTIVES: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. METHODS: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). RESULTS: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10% false discovery rate. CONCLUSIONS: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

Original languageEnglish
Article numbere90
Number of pages10
JournalClinical and Translational Gastroenterology
Volume6
Early online date4 May 2015
DOIs
Publication statusPublished - 18 Jun 2015

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Constipation
Opioid Analgesics
Laxatives
Neoplasms
Single Nucleotide Polymorphism
Karnofsky Performance Status
Neoplasm Metastasis
Individuality
Patient Care
Hospitalization
Body Mass Index
Regression Analysis
Therapeutics
Genes

ASJC Scopus subject areas

  • Gastroenterology

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Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids. / Laugsand, Eivor A. (Corresponding Author); Skorpen, Frank; Kaasa, Stein; Sabatowski, Rainer; Strasser, Florian; Fayers, Peter; Klepstad, Pål.

In: Clinical and Translational Gastroenterology, Vol. 6, e90, 18.06.2015.

Research output: Contribution to journalArticle

Laugsand, Eivor A. ; Skorpen, Frank ; Kaasa, Stein ; Sabatowski, Rainer ; Strasser, Florian ; Fayers, Peter ; Klepstad, Pål. / Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids. In: Clinical and Translational Gastroenterology. 2015 ; Vol. 6.
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title = "Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids",
abstract = "OBJECTIVES: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. METHODS: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). RESULTS: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10{\%} false discovery rate. CONCLUSIONS: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.",
author = "Laugsand, {Eivor A.} and Frank Skorpen and Stein Kaasa and Rainer Sabatowski and Florian Strasser and Peter Fayers and P{\aa}l Klepstad",
note = "Acknowledgments. We are grateful to all the researchers involved in The European Pharmacogenetic Opioid Study (EPOS) and to Gunnhild Jakobsen who organized the collection of data.",
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T1 - Genetic and Non-genetic Factors Associated With Constipation in Cancer Patients Receiving Opioids

AU - Laugsand, Eivor A.

AU - Skorpen, Frank

AU - Kaasa, Stein

AU - Sabatowski, Rainer

AU - Strasser, Florian

AU - Fayers, Peter

AU - Klepstad, Pål

N1 - Acknowledgments. We are grateful to all the researchers involved in The European Pharmacogenetic Opioid Study (EPOS) and to Gunnhild Jakobsen who organized the collection of data.

PY - 2015/6/18

Y1 - 2015/6/18

N2 - OBJECTIVES: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. METHODS: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). RESULTS: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10% false discovery rate. CONCLUSIONS: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

AB - OBJECTIVES: To examine whether the inter-individual variation in constipation among patients receiving opioids for cancer pain is associated with genetic or non-genetic factors. METHODS: Cancer patients receiving opioids were included from 17 centers in 11 European countries. Intensity of constipation was reported by 1,568 patients on a four-point categorical scale. Non-genetic factors were included as covariates in stratified regression analyses on the association between constipation and 75 single-nucleotide polymorphisms (SNPs) within 15 candidate genes related to opioid- or constipation-signaling pathways (HTR3E, HTR4, HTR2A, TPH1, ADRA2A, CHRM3, TACR1, CCKAR, KIT, ARRB2, GHRL, ABCB1, COMT, OPRM1, and OPRD1). RESULTS: The non-genetic factors significantly associated with constipation were type of laxative, mobility and place of care among patients receiving laxatives (N=806), in addition to Karnofsky performance status and presence of metastases among patients not receiving laxatives (N=762) (P<0.01). Age, gender, body mass index, cancer diagnosis, time on opioids, opioid dose, and type of opioid did not contribute to the inter-individual differences in constipation. Five SNPs, rs1800532 in TPH1, rs1799971 in OPRM1, rs4437575 in ABCB1, rs10802789 in CHRM3, and rs2020917 in COMT were associated with constipation (P<0.01). Only rs2020917 in COMT passed the Benjamini-Hochberg criterion for a 10% false discovery rate. CONCLUSIONS: Type of laxative, mobility, hospitalization, Karnofsky performance status, presence of metastases, and five SNPs within TPH1, OPRM1, ABCB1, CHRM3, and COMT may contribute to the variability in constipation among cancer patients treated with opioids. Knowledge of these factors may help to develop new therapies and to identify patients needing a more individualized approach to treatment.

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U2 - 10.1038/ctg.2015.19

DO - 10.1038/ctg.2015.19

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VL - 6

JO - Clinical and Translational Gastroenterology

JF - Clinical and Translational Gastroenterology

SN - 2155-384X

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