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Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.
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  • Martin Houston,
  • Una McMenamin,
  • Brian Johnston,
  • Ronald McDowell,
  • Carmel Hughes,
  • Peter Murchie,
  • C Cardwell
Martin Houston
Queen's University Belfast Centre for Public Health
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Una McMenamin
Queen's University Belfast Centre for Public Health
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Brian Johnston
Royal Victoria Hospital
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Ronald McDowell
Queen's University Belfast Centre for Public Health
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Carmel Hughes
Queen's University of Belfast School of Pharmacy
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Peter Murchie
University of Aberdeen Institute of Applied Health Sciences
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C Cardwell
Queen's University Belfast Centre for Public Health
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Abstract

Background 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. 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=2,432), gastric (n=1,443), and colorectal cancer (n=8,750) 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 (OR) and 95% confidence intervals (CI) 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). Conclusion 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.
05 Aug 2022Submitted to British Journal of Clinical Pharmacology
08 Aug 2022Assigned to Editor
08 Aug 2022Submission Checks Completed
09 Aug 2022Reviewer(s) Assigned
02 Sep 2022Review(s) Completed, Editorial Evaluation Pending
08 Sep 2022Editorial Decision: Revise Major