Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies

Martin Houston; Úna McMenamin; Brian Johnston; Ronald McDowell; Carmel Hughes; Peter Murchie; Christopher Cardwell

doi:10.1111/bcp.15759

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies

Martin Houston^* (Corresponding Author), Úna McMenamin, Brian Johnston, Ronald McDowell, Carmel Hughes, Peter Murchie, Christopher Cardwell

^*Corresponding author for this work

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

Abstract

There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract.

Methods
A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use.

Results
There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively).

Conclusions
In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Original language	English
Pages (from-to)	2757-2766
Number of pages	10
Journal	British Journal of Clinical Pharmacology
Volume	89
Issue number	9
Early online date	18 May 2023
DOIs	https://doi.org/10.1111/bcp.15759
Publication status	Published - Sept 2023

Bibliographical note

Acknowledgements:
We wish to thank PCCIUR, University of Aberdeen, especially Artur Wozniak, for
extracting the data and performing case-control matching. This work was supported by Cancer Research UK (reference C37316/A25535). ÚMcM is supported by a UKRI Future Leaders Fellowship (MR/T019859/1). The sponsors had no involvement with the planning, execution, or completion of the study

Data Availability Statement

The data that support the findings of this study are available from the Institute of Applied Health Sciences, University of Aberdeen. Restrictions apply to the availability of these data, which were used under licence for this study. Data are available from the authors with the permission of the Institute of Applied Health Sciences Section.

Additional supporting information can be found online in the Supporting Information section at the end of this article.

Keywords

Opioids
Codeine
Dihydrocodeine
Gastrointestinal neoplasms
Oesophageal cancer
Gastric cancer
Colorectal cancer
Gastrointestinal Motility

UN SDGs

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

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Houston_etal_BJCP_Exposure_To_Weak_VOR
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Cite this

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title = "Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies",

abstract = "There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract.MethodsA series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use.ResultsThere was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively).ConclusionsIn this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.",

keywords = "Opioids, Codeine, Dihydrocodeine, Gastrointestinal neoplasms, Oesophageal cancer, Gastric cancer, Colorectal cancer, Gastrointestinal Motility",

author = "Martin Houston and {\'U}na McMenamin and Brian Johnston and Ronald McDowell and Carmel Hughes and Peter Murchie and Christopher Cardwell",

note = "Acknowledgements: We wish to thank PCCIUR, University of Aberdeen, especially Artur Wozniak, for extracting the data and performing case-control matching. This work was supported by Cancer Research UK (reference C37316/A25535). {\'U}McM is supported by a UKRI Future Leaders Fellowship (MR/T019859/1). The sponsors had no involvement with the planning, execution, or completion of the study",

year = "2023",

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doi = "10.1111/bcp.15759",

language = "English",

volume = "89",

pages = "2757--2766",

journal = "British Journal of Clinical Pharmacology",

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}

TY - JOUR

T1 - Exposure to weak opioids and risk of gastrointestinal tract cancers

T2 - A series of nested case-control studies

AU - Houston, Martin

AU - McMenamin, Úna

AU - Johnston, Brian

AU - McDowell, Ronald

AU - Hughes, Carmel

AU - Murchie, Peter

AU - Cardwell, Christopher

N1 - Acknowledgements: We wish to thank PCCIUR, University of Aberdeen, especially Artur Wozniak, for extracting the data and performing case-control matching. This work was supported by Cancer Research UK (reference C37316/A25535). ÚMcM is supported by a UKRI Future Leaders Fellowship (MR/T019859/1). The sponsors had no involvement with the planning, execution, or completion of the study

PY - 2023/9

Y1 - 2023/9

N2 - There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract.MethodsA series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use.ResultsThere was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively).ConclusionsIn this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

AB - There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract.MethodsA series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use.ResultsThere was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively).ConclusionsIn this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

KW - Opioids

KW - Codeine

KW - Dihydrocodeine

KW - Gastrointestinal neoplasms

KW - Oesophageal cancer

KW - Gastric cancer

KW - Colorectal cancer

KW - Gastrointestinal Motility

U2 - 10.1111/bcp.15759

DO - 10.1111/bcp.15759

M3 - Article

C2 - 37117154

SN - 0306-5251

VL - 89

SP - 2757

EP - 2766

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 9

ER -

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies

Abstract

Bibliographical note

Data Availability Statement

Keywords

UN SDGs

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