Abstract
Although hydrochlorothiazide (HCTZ) has been suggested to increase skin cancer risk in white Westerners, there is scant evidence for the same in Asians. We analyzed the association between the use of hydrochlorothiazide and non-melanoma in the Asian population using the common data model. Methods: A retrospective multicenter observational study was conducted using a distributed research network to analyze the effect of HCTZ on skin cancer from 2004 to 2018. We performed Cox regression to evaluate the effects by comparing the use of HCTZ with other antihypertensive drugs. All analyses were re-evaluated using matched data using the propensity score matching (PSM). Then, the overall effects were evaluated by combining results with the meta-analysis. Results: Positive associations were observed in the use of HCTZ with high cumulative dose for non-melanoma skin cancer (NMSC) in univariate analysis prior to the use of PSM. Some negative associations were observed in the use of low and medium cumulative doses. Conclusion: Although many findings in our study were inconclusive, there was a non-significant association of a dose-response pattern with estimates increasing in cumulative dose of HCTZ. In particular, a trend with a non-significant positive association was observed with the high cumulative dose of HCTZ.
Highlights
Hypertension is a major risk factor for non-communicable diseases (NCDs), such as cardiovascular and renal diseases [1,2]
Gandini et al reported in their meta-analysis that they found no association between thiazide diuretics and skin cancer [18]
We investigated the association between HCTZ and skin cancer, including melanoma and non-melanoma skin cancer (NMSC) by using the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM)-based distributed research network
Summary
Hypertension is a major risk factor for non-communicable diseases (NCDs), such as cardiovascular and renal diseases [1,2]. Thiazide or thiazide-like diuretics are considered as one of the first-line classes in antihypertensive pharmacotherapy They are essential in combination therapy as volume and sodium retention is the main mechanism in treatment-resistant hypertension [10,11,12]. Gandini et al reported in their meta-analysis that they found no association between thiazide diuretics and skin cancer [18] These inconsistent and uncertain observations between studies emphasize the challenges we face when interpreting the findings in real-world observational studies. To elucidate the association between the use of HCTZ and skin cancer clearly, a nationwide observational study with qualified assessment and fewer biases should be conducted through a distributed data system with standardized protocol. By processing all analyses in the CDM network with a standardized code, we validated the utility of the CDM network for quick and reliable big data-based clinical observational research examining the potential carcinogenic risk of drugs
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