4B-02 - Analgesic Use and Risk of Renal Cell Carcinoma: Prospective Analysis in the Health Professionals Follow-up Study

Background: Analgesics, including aspirin, acetaminophen, and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), are the most commonly consumed over-the-counter drugs worldwide. Analgesics may either protect against or increase the risk of several malignancies. However, existing studies examining whether analgesics play a role in renal cell carcinoma (RCC) development have yielded mixed results.

Objectives: To investigate the association between analgesic use and RCC risk in men, using data from the Health Professionals Follow-up Study (HPFS).

Methods: The prospective HPFS cohort is comprised of 51,529 male health professionals who were aged 40 to 75 years at baseline in 1986. Information on the use of analgesics was collected longitudinally on biennial questionnaires from 1986 to 2018. Multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between regular use (≥2 times/week) of aspirin, acetaminophen, and non-aspirin NSAIDs, and the risk of pathology-confirmed RCC. These associations were further examined based on tumor characteristics, including stage, grade, and histology, and pre-defined risk factor subgroups, such as hypertension, diabetes, obesity, and smoking status. Dose-response relationships for each analgesic were assessed based on the cumulative duration, frequency, and quantity of regular use.

Results: During over 30 years of follow-up among 49,414 men, 310 RCC cases occurred. Regular use of aspirin, acetaminophen, and non-aspirin NSAIDs was not associated with an increased risk of RCC compared to non-regular use. Similar results were observed across tumor characteristics and subgroups, except for hypertension. Acetaminophen use was associated with a 2.29-fold increased risk of RCC in men without hypertension (95% CI: 1.31-4.02), but not in those with hypertension (p-interaction=0.04). Dose-response relationships were observed between non-aspirin NSAIDs use and RCC risk by cumulative duration (≥10 years vs no use: HR=1.82, 95% CI: 1.08-3.07, p-trend=0.02) and quantity (≥15 tablets/week: HR=1.54, 95% CI: 1.04-2.28, p-trend=0.04).

Conclusions: Regular use of analgesics was not associated with a higher risk of RCC in men from the HPFS cohort. Longer duration or higher intake of regular non-aspirin NSAIDs use may be associated with an increased risk of RCC. These associations could vary based on patient characteristics, such as hypertension.