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

Research output: Contribution to journalArticle

Abstract

Purpose: The strong male predominance of gastro-oesophageal cancer suggests 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 2,003 gastro-oesophageal cancer cases and 9,650 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=0.071) or finasteride (adjusted OR=0.49; 95% CI 0.24, 0.99; p-value=0.046).

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
JournalPharmacoepidemiology and Drug Safety
Publication statusAccepted/In press - 17 Sep 2019

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

Keywords

  • gastric cancer
  • oesophageal cancer
  • Androgen
  • 5α-reductase inhibitor

Cite this

Busby, J., Karasneh, R., Murchie, P., McMenamin, Ú., Gadalla, S. M., Camargo, M. C., ... Cardwell, C. R. (Accepted/In press). The role of 5α-reductase inhibitors in gastro-oesophageal cancer risk: a nested case-control study. Pharmacoepidemiology and Drug Safety.

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, 17.09.2019.

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. 2019.
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abstract = "Purpose: The strong male predominance of gastro-oesophageal cancer suggests 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 2,003 gastro-oesophageal cancer cases and 9,650 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=0.071) or finasteride (adjusted OR=0.49; 95{\%} CI 0.24, 0.99; p-value=0.046).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.",
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T2 - a nested case-control study

AU - Busby, John

AU - Karasneh, Reema

AU - Murchie, Peter

AU - McMenamin, Úna

AU - Gadalla, Shahinaz M.

AU - Camargo, M. Constanza

AU - Iversen, Lisa

AU - Lee, Amanda J.

AU - Spence, Andrew D.

AU - Cardwell, Chris R.

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N2 - Purpose: The strong male predominance of gastro-oesophageal cancer suggests 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 2,003 gastro-oesophageal cancer cases and 9,650 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=0.071) or finasteride (adjusted OR=0.49; 95% CI 0.24, 0.99; p-value=0.046).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.

AB - Purpose: The strong male predominance of gastro-oesophageal cancer suggests 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 2,003 gastro-oesophageal cancer cases and 9,650 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=0.071) or finasteride (adjusted OR=0.49; 95% CI 0.24, 0.99; p-value=0.046).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.

KW - gastric cancer

KW - oesophageal cancer

KW - Androgen

KW - 5α-reductase inhibitor

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JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

ER -