The average age of participants at index date was 72.5 years ± 8.6 SD (range: 43–85). The majority of participants were male (n=514, 61.9%). Compared to controls, cases were more likely to have red or blond hair, blue or grey eyes, and lighter skin types. Cases were also more likely to report current smoking, a family history of skin cancer and a history of childhood freckles, routine sun exposure and severe sunburns ().
Distribution of Risk Factors for Cutaneous Squamous Cell Carcinomas among Cases and Controls
The majority of study participants (60.8%) self-reported regular use of NSAID in the 10 years prior to baseline. The most commonly reported regularly used NSAIDs were aspirin (48%), ibuprofen (18%), naproxen (5%), and nabumetone (4%). Other NSAIDs (bismuth subsalicylate, diclofenac, etodolac, indomethacin, piroxicam, salsalate, sulindac, celecoxib, rofecoxib, and valdecoxib) were regularly used by less than 2% of the participants. Acetaminophen was regularly used by 19% of participants. There were no significant differences in sex, age at index date, or any measured SCC risk factors between regular and non-users of any NSAID. Regular NSAID users were more likely to take acetaminophen (p=0.005). There were no significant differences in reported type of NSAID regularly used between cases and controls except that seven cases reported regular celecoxib use compared to only one control.
Regular use of any NSAID was not associated with a reduction in SCC risk (fully adjusted OR=1.32, 95% CI: 0.92–1.89, ). Although NSAID users whose exposure was of short duration (1–3 years) appeared to be at somewhat increased risk for SCC (adjusted OR=1.94, 95% CI: 1.10–3.44), we found no consistent effects of duration of use of any NSAID on SCC risk (p for linear trend 0.69). In comparing regular aspirin users to non-users, there was no negative association with SCC risk (adjusted OR=1.38, 95% CI: 0.96–1.97). Duration of aspirin use was also not associated with SCC risk (p for trend 0.52). High-dose aspirin users did not have a different SCC risk than low-dose users. Regular ibuprofen users had a non-significant slightly lower risk of SCC than never/occasional users (adjusted OR=0.74, 95% CI: 0.46–1.19). Although there were no consistent effects of dose or duration, all ORs suggested a protective association with ibuprofen exposure. Among non-aspirin NSAIDs, there was also no significant SCC risk reduction (adjusted OR 0.84, 95% CI: 0.56–1.26). For all four of our exposure variables, we found no evidence of a dose-response effect by duration of use. As expected, there was no association between regular use of acetaminophen (the control medication without COX activity) and SCC risk (OR=1.15; 95% CI: 0.74–1.81) nor any association between dose and duration of acetaminophen use.
Self-Reported NSAID use among Cases and Controls
We examined which of the co-variables served as potential confounding factors by virtue of being associated with both NSAID use and SCC risk at the p≤.20 level. Only two variables emerged as potential confounding variables: hair color and occupational sun exposure. We analyzed all multivariate models using only those two potential confounding variables (parsimonious multivariable model) and found no significant associations between NSAID use (categorized as any NSAID, aspirin, ibuprofen, non-aspirin NSAIDs) and SCC risk (data not shown). Of note, the slightly protective effect of ibuprofen use on SCC risk was not evident in the parsimonious multivariable model (adjusted OR: 1.03, 95% CI: 0.71–1.50).
Finally, we examined the association of pharmacy-dispensed NSAIDs and SCC risk. In total, 27% of cases and 26% of controls were prescribed an NSAID (not including aspirin, ibuprofen or naproxen) and had refilled the prescription for the NSAID at least once during the 10-year observation period. There was no association between any pharmacy dispensed NSAID use and SCC risk whether examining overall NSAIDs, or examining individual NSAID types (ever/never use). There was also no statistically significant effect of duration ().
Pharmacy-Dispensed NSAID Exposure among Cases and Controls@