Department of Research, Cancer Registry of Norway, Oslo, Norway.
Section for Colorectal Cancer Screening, Cancer Registry of Norway, Oslo, Norway.
Cancer Epidemiol Biomarkers Prev. 2021 Apr;30(4):682-689. doi: 10.1158/1055-9965.EPI-20-1028. Epub 2020 Nov 3.
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..
基于人群的药物流行病学研究用于评估上市后药物安全性并发现药物超适应证使用的有益效果。我们进行了一项药物广泛关联研究（DWAS），以筛选处方药与癌症风险之间的关联。
这项基于登记的、巢式病例对照研究，按年龄、性别和病例诊断日期进行 1:10 配对，包括大约 200 万挪威居民，以及他们 2004 年至 2014 年的药物使用史。我们评估了根据解剖治疗化学（ATC）分类系统分类的处方药与 15 种最常见癌症类型的风险之间的关联，包括总体和组织学。我们使用分层 Cox 回归，调整了其他药物使用、合并症、县和产次，并探索了剂量反应趋势。
我们在 ATC2 水平上发现了 1230 种药物-癌症组合中的 145 种关联，在 ATC4 水平上发现了 8130 种中的 77 种。本文和在线工具（https://pharmacoepi.shinyapps.io/drugwas/）展示了所有药物-癌症组合的结果。一些关联以前已经报道过，例如，更年期激素与乳腺癌风险的关联，或者可能存在混杂因素，例如慢性阻塞性肺疾病与肺癌风险的关联。其他关联是新的，例如质子泵抑制剂与黑色素瘤风险的负相关，以及推进剂与肺癌风险的致癌关联。
这项研究证实了以前报道的关联，并对处方药可能的致癌或化学预防作用产生了新的假设。这种探索性方法的结果需要在定制的流行病学和临床前研究中进行验证。
DWAS 研究是定义新的药物-癌症假设的强大而重要的工具。
