The role of 5α‐reductase inhibitors in gastro‐oesophageal cancer risk: A nested case‐control study

John Busby* (Corresponding Author), Reema Karasneh, Peter Murchie, Úna McMenamin, Shahinaz M. Gadalla, M. Constanza Camargo, Lisa Iversen, Amanda J. Lee, Andrew D. Spence, Chris R. Cardwell

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Purpose
The strong male predominance of gastro‐oesophageal cancer suggests that sex hormones play an important role. 5α‐Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro‐oesophageal cancer risk.

Methods
We conducted a nested case‐control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use.

Results
The study included 2003 gastro‐oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro‐oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56‐1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50‐0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27‐1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24‐0.99; P value = .046).

Conclusions
We found evidence of reduced gastro‐oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.
Original languageEnglish
Pages (from-to)48-56
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Volume29
Issue number1
Early online date12 Nov 2019
DOIs
Publication statusPublished - Jan 2020

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Finasteride
Odds Ratio
Neoplasms
Electronic Prescribing
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Androgen Antagonists
Proton Pump Inhibitors
Gonadal Steroid Hormones
Esophageal Neoplasms
General Practice
Aspirin
Stomach Neoplasms
Comorbidity
Epidemiologic Studies
Primary Health Care
Randomized Controlled Trials
Logistic Models
Cell Proliferation
Parturition
Databases

Keywords

  • gastric cancer
  • oesophageal cancer
  • Androgen
  • 5α-reductase inhibitor
  • ANDROGEN RECEPTOR
  • androgen
  • ADENOCARCINOMA
  • FINASTERIDE
  • BARRETTS-ESOPHAGUS
  • 5 alpha-reductase inhibitor
  • SEX-HORMONE RECEPTORS
  • GASTRIC-CANCER
  • CELL-MIGRATION
  • PROSTATE-CANCER
  • ESOPHAGEAL CANCER
  • EXPRESSION

Cite this

The role of 5α‐reductase inhibitors in gastro‐oesophageal cancer risk : A nested case‐control study. / Busby, John (Corresponding Author); Karasneh, Reema; Murchie, Peter; McMenamin, Úna; Gadalla, Shahinaz M.; Camargo, M. Constanza; Iversen, Lisa; Lee, Amanda J.; Spence, Andrew D.; Cardwell, Chris R.

In: Pharmacoepidemiology and Drug Safety, Vol. 29, No. 1, 01.2020, p. 48-56.

Research output: Contribution to journalArticle

Busby, John ; Karasneh, Reema ; Murchie, Peter ; McMenamin, Úna ; Gadalla, Shahinaz M. ; Camargo, M. Constanza ; Iversen, Lisa ; Lee, Amanda J. ; Spence, Andrew D. ; Cardwell, Chris R. / The role of 5α‐reductase inhibitors in gastro‐oesophageal cancer risk : A nested case‐control study. In: Pharmacoepidemiology and Drug Safety. 2020 ; Vol. 29, No. 1. pp. 48-56.
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AU - Gadalla, Shahinaz M.

AU - Camargo, M. Constanza

AU - Iversen, Lisa

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N2 - PurposeThe strong male predominance of gastro‐oesophageal cancer suggests that sex hormones play an important role. 5α‐Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro‐oesophageal cancer risk.MethodsWe conducted a nested case‐control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use.ResultsThe study included 2003 gastro‐oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro‐oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56‐1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50‐0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27‐1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24‐0.99; P value = .046).ConclusionsWe found evidence of reduced gastro‐oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.

AB - PurposeThe strong male predominance of gastro‐oesophageal cancer suggests that sex hormones play an important role. 5α‐Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro‐oesophageal cancer risk.MethodsWe conducted a nested case‐control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use.ResultsThe study included 2003 gastro‐oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro‐oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56‐1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50‐0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27‐1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24‐0.99; P value = .046).ConclusionsWe found evidence of reduced gastro‐oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.

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