Drug use and cancer risk: a drug-wide association study (DWAS) in Norway.

Background Population-based pharmacoepidemiological studies are used to assess post-marketing 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 2004-2014. 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 1230 drug-cancer combinations on the ATC2-level and 77 of 8130 on the ATC4-level. Results for all drug-cancer combinations are presented in this paper and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, i.e. menopausal hormones and breast cancer risk, or are likely confounded, i.e. chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, i.e. 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 epidemiological and preclinical studies. Impact DWAS studies are robust and important tools to define new drug-cancer hypotheses.