Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway.


Journal

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
ISSN: 1538-7755
Titre abrégé: Cancer Epidemiol Biomarkers Prev
Pays: United States
ID NLM: 9200608

Informations de publication

Date de publication:
04 2021
Historique:
received: 03 08 2020
revised: 11 09 2020
accepted: 22 10 2020
pubmed: 5 11 2020
medline: 26 8 2021
entrez: 4 11 2020
Statut: ppublish

Résumé

Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk. This registry-based, nested case-control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose-response trends. We found 145 associations among 1,230 drug-cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug-cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk. This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies. DWAS studies are robust and important tools to define new drug-cancer hypotheses.

Sections du résumé

BACKGROUND
Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk.
METHODS
This registry-based, nested case-control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose-response trends.
RESULTS
We found 145 associations among 1,230 drug-cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug-cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk.
CONCLUSIONS
This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies.
IMPACT
DWAS studies are robust and important tools to define new drug-cancer hypotheses.

Identifiants

pubmed: 33144282
pii: 1055-9965.EPI-20-1028
doi: 10.1158/1055-9965.EPI-20-1028
doi:

Substances chimiques

Pharmaceutical Preparations 0

Types de publication

Journal Article Comment

Langues

eng

Sous-ensembles de citation

IM

Pagination

682-689

Commentaires et corrections

Type : CommentIn
Type : CommentOn

Informations de copyright

©2020 American Association for Cancer Research.

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Auteurs

Nathalie C Støer (NC)

Department of Research, Cancer Registry of Norway, Oslo, Norway.

Edoardo Botteri (E)

Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.

G Hege Thoresen (GH)

Department of Pharmacology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Pharmacy, Section for Pharmacology and Pharmaceutical Biosciences, University of Oslo, Oslo, Norway.

Øystein Karlstad (Ø)

Department of Chronic Diseases and Ageing, Norwegian Institute of Public Health, Oslo, Norway.

Elisabete Weiderpass (E)

International Agency for Research on Cancer, World Health Organization, Lyon, France.

Søren Friis (S)

Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark.

Anton Pottegård (A)

Department of Public Health, Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark.

Bettina K Andreassen (BK)

Department of Research, Cancer Registry of Norway, Oslo, Norway. b.k.andreassen@kreftregisteret.no.

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