Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases

Andrew D Spence; John  Busby; Peter Murchie; Andrew T Kunzmann; Úna C McMenamin; Helen G Coleman; Brian T Johnston; Michael A O'Rorke; Liam J Murray; Lisa Iversen; Amanda Jane Lee; Chris R Cardwell

doi:10.1002/ijc.31293

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases

Andrew D Spence (Corresponding Author), John Busby, Peter Murchie, Andrew T Kunzmann, Úna C McMenamin, Helen G Coleman, Brian T Johnston, Michael A O'Rorke, Liam J Murray, Lisa Iversen, Amanda Jane Lee, Chris R Cardwell

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Abstract

Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation.

Original language	English
Pages (from-to)	22-31
Number of pages	11
Journal	International Journal of Cancer
Volume	143
Issue number	1
Early online date	8 Mar 2018
DOIs	https://doi.org/10.1002/ijc.31293
Publication status	Published - 1 Jul 2018

Bibliographical note

Acknowledgements
We acknowledge collaboration with the Research Applications and Data Management Team lead by Ms Katie Wilde, University of Aberdeen in conducting our study. This research has been conducted using the UK Bio-bank Resource under application number 34374.

Keywords

β2 agonists
Oesophageal cancer
Benzodiazepines
Calcium channel blockers
Nitrates

UN SDGs

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

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Accepted Manuscript
This is the peer reviewed version of the following article: Spence, AD, Busby, J, Murchie, P, Kunzmann, AT, McMenamin, ÚC, Coleman, HG, Johnston, BT, O'Rorke, MA, Murray, LJ, Iversen, L, Lee, AJ & Cardwell, CR 2018, 'Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases' International Journal of Cancer, vol 143, no. 1, pp. 22-31 , which has been published in final form at DOI: 10.1002/ijc.31293. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript, 305 KBLicence: Unspecified

Peter Murchie, BSc (Med Sci), MBChB, MSc, MRCGP, CertMgmt (Open), PhD
- School of Medicine, Medical Sciences & Nutrition, Applied Health Sciences - Personal Chair (Clinical)
- Institute of Applied Health Sciences
Person: Clinical Academic

Cite this

Spence, A. D., Busby, J., Murchie, P., Kunzmann, A. T., McMenamin, Ú. C., Coleman, H. G., Johnston, B. T., O'Rorke, M. A., Murray, L. J., Iversen, L., Lee, A. J., & Cardwell, C. R. (2018). Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases. International Journal of Cancer, 143(1), 22-31. https://doi.org/10.1002/ijc.31293

Spence, AD, Busby, J, Murchie, P, Kunzmann, AT, McMenamin, ÚC, Coleman, HG, Johnston, BT, O'Rorke, MA, Murray, LJ, Iversen, L , Lee, AJ & Cardwell, CR 2018, 'Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases', International Journal of Cancer, vol. 143, no. 1, pp. 22-31. https://doi.org/10.1002/ijc.31293

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title = "Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases",

abstract = "Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation. ",

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note = "Acknowledgements We acknowledge collaboration with the Research Applications and Data Management Team lead by Ms Katie Wilde, University of Aberdeen in conducting our study. This research has been conducted using the UK Bio-bank Resource under application number 34374.",

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AU - McMenamin, Úna C

AU - Coleman, Helen G

AU - Johnston, Brian T

AU - O'Rorke, Michael A

AU - Murray, Liam J

AU - Iversen, Lisa

AU - Lee, Amanda Jane

AU - Cardwell, Chris R

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N2 - Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation.

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IS - 1

ER -

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases

Abstract

Bibliographical note

Keywords

UN SDGs

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Peter Murchie, BSc (Med Sci), MBChB, MSc, MRCGP, CertMgmt (Open), PhD

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