title: The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk: a nested case-control study of routine Scottish data.
abstract: Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro-oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro-oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case-control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro-oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro-oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose-response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro-oesophageal cancer. Our findings should reassure GPs and patients that these widely-used medications are safe with respect to gastro-oesophageal cancer risk.
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Busby
authors.affiliation: Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Murchie
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Liam
authors.initials: L
authors.lastname: Murray
authors.affiliation: Academic Primary Care, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Medical Statistics Team, Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Lee
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Spence
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, United Kingdom.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Watson
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Chris R
authors.initials: CR
authors.lastname: Cardwell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications* / Q000188:drug therapy; D012307:Risk Factors; D012606:Scotland; D013148:Spironolactone / Q000009:adverse effects / Q000627:therapeutic use; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000473:pathology; D013752:Tetracycline / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D004164:Diphosphonates; D013148:Spironolactone; D013752:Tetracycline
keywords: case-control studies; esophageal cancer; gastric cancer; inflammation; risk factors