Association between hydrochlorothiazide exposure and skin and lip cancer: a series of populationbased nested case-control studies

Study type

• Study topic:
  Human medicinal product

  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C09DX01) valsartan, amlodipine and hydrochlorothiazide

  valsartan, amlodipine and hydrochlorothiazide

  (C09BX03) ramipril, amlodipine and hydrochlorothiazide

  ramipril, amlodipine and hydrochlorothiazide

  (C09DX03) olmesartan medoxomil, amlodipine and hydrochlorothiazide

  olmesartan medoxomil, amlodipine and hydrochlorothiazide

  (C03AX01) hydrochlorothiazide, combinations

  hydrochlorothiazide, combinations

  (C03EA01) hydrochlorothiazide and potassium-sparing agents

  hydrochlorothiazide and potassium-sparing agents

  (C03AB03) hydrochlorothiazide and potassium

  hydrochlorothiazide and potassium

  (C03AA03) hydrochlorothiazide

  hydrochlorothiazide

  (C09XA54) aliskiren, amlodipine and hydrochlorothiazide

  aliskiren, amlodipine and hydrochlorothiazide

  (C09XA52) aliskiren and hydrochlorothiazide

  aliskiren and hydrochlorothiazide
• Medical condition to be studied:
  Skin cancer

Population studied

• Short description of the study population:
  Patients were required to have no previous cancer diagnosis before the index date, i.e. the date of the first skin cancer event occurring after cohort entry for case subjects. For the lip cancer and oral cavity cancer analysis, patients were allowed to have a prior history of nonmelanoma skin cancer (BCC or SCC), in keeping with the Danish study. Patients were required to have no prior record of organ transplantation, human immunodeficiency virus diagnosis or use of immunosuppressant drugs such as azathioprine, cyclosporine or mycophenolate mofetil, at any time before the index date that may predispose to skin cancer risk.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  50000

Study design details

• Main study objective:
  a) Assessing the association between hydrochlorothiazide exposure and each skin and lip cancer outcome using patients in THIN.b) Assessing if the association is influenced by adjusting for additional confounders such as smoking status and body mass index.
• Outcomes:
  1. Lip cancer2. Squamous cell carcinoma skin cancer3. Basal cell carcinoma skin cancer4. Melanoma
• Data analysis plan:
  Cases will be identified through Read codes recorded in THIN and the incidence of these conditions calculated among the population. Incidence density sampling will be used to randomly select controls to each matched on age, sex, general practice and follow up time and will repeated for each cancer case. Up to 100 controls will be selected for lip cancer and up to 20 controls for the other cancer outcomes. Odds ratios will be estimated for the association between ever use and cumulative use of hydrochlorothiazide exposure prior to the index date, using a primary lag time of exposure of two years.

Documents

Study results

bcp.14245

Study publications

Morales DR, Pacurariu A, Slattery J, Kurz X. Association between hydrochlorothi…