Abstract 5893: Analgesic use and renal cell carcinoma incidence and survival: Results from three prospective cohort studies
Authors: Graff Rebecca E. , Sanchez Alejandro , Choueiri Toni K. , Stampfer Meir J. , Giovannucci Edward L. , Mucci Lorelei A. , Cho Eunyoung , Preston Mark A. 
Published: June 2022

Abstract
Background: Analgesics are the most commonly consumed over-the-counter drugs worldwide. Considerable evidence suggests a beneficial effect of analgesics, and especially aspirin, on cardiovascular disease and colorectal cancer risk. Studies examining whether widely used analgesics - aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen - play a role in renal cell carcinoma (RCC) have yielded mixed results.
Methods: We examined associations between pre-diagnostic analgesic use and incidence of total and fatal RCC in the Health Professionals Follow-up Study (HPFS; 1986-2016), Nurses’ Health Study (NHS; 1980-2016 for aspirin; 1990-2016 for non-aspirin NSAIDs and acetaminophen), and Nurses’ Health Study 2 (NHS2; 1989-2015; total RCC only). Information on use of aspirin, non-aspirin NSAIDs, and acetaminophen was collected longitudinally on biennial questionnaires. We used Cox proportional hazards models to estimate cohort-specific, multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) according to current use (updated in each questionnaire period) and, separately, duration of use (since study baseline) of each analgesic. Results across cohorts were combined using random-effects meta-analyses. We also used Cox regression to evaluate post-diagnostic analgesic use with respect to RCC-specific mortality among RCC cases in the pooled HPFS and NHS cohorts.
Results: Among 259,545 participants, 796 incident RCC cases were diagnosed. Neither current nor duration of pre-diagnostic use of any of the analgesics was associated with the risk of total RCC in meta-analyses of the three study cohorts. For fatal RCC (n=175 cases), however, meta-analyses of the HPFS and NHS suggested covariate-adjusted positive associations with current (HR: 1.37, 95% CI: 0.96-1.96, p-heterogeneity: 0.80) and duration of (HR&gt;10yrs vs. Never: 2.62, 95% CI: 1.23-5.58, p-trend: 0.006, p-heterogeneity: 0.30) pre-diagnostic non-aspirin NSAID use. In addition, in the HPFS only, current (HR: 2.35, 95% CI: 1.33-4.17) and duration of (HR&gt;10yrs vs. Never: 1.83, 95% CI: 0.42-7.93, p-trend: 0.07) pre-diagnostic acetaminophen use indicated positive associations with fatal RCC. Analyses of RCC-specific mortality among participants diagnosed with RCC demonstrated an inverse association with current post-diagnostic aspirin use (HR: 0.68, 95% CI: 0.48-0.97), but not duration of post-diagnostic aspirin use (HR&gt;10yrs vs. Never: 0.89, 95% CI: 0.53-1.51, p-trend: 0.98). Analgesics were not otherwise associated with RCC survival.
Conclusions: Our findings support a potential positive association between non-aspirin NSAID use and incident fatal RCC. It remains possible that analgesics may operate differently in the setting of RCC from the context of other chronic diseases.
Citation Format: Rebecca E. Graff, Alejandro Sanchez, Toni K. Choueiri, Meir J. Stampfer, Edward L. Giovannucci, Lorelei A. Mucci, Eunyoung Cho, Mark A. Preston. Analgesic use and renal cell carcinoma incidence and survival: Results from three prospective cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5893.