Objective To assess associations between Parkinson disease (PD) and putatively protective factors—smoking, caffeine (coffee, tea, and soft drinks), and nonsteroidal anti-inflammatory drugs (aspirin, ibuprofen, and naproxen).<br><br>Design Family-based case-control study.<br><br>Setting Academic medical center clinic.<br><br>Participants A total of 356 case subjects and 317 family controls who self-reported environmental exposures.<br><br>Main Outcome Measures Associations between PD and environmental measures (history, status, dosage, duration, and intensity) of smoking, coffee, caffeine, nonsteroidal anti-inflammatory drugs, and nonaspirin nonsteroidal anti-inflammatory drugs were examined using generalized estimating equations with an independent correlation matrix while controlling for age and sex.<br><br>Results Individuals with PD were significantly less likely to report ever smoking (odds ratio = 0.56; 95% confidence interval, 0.41-0.78). Additional measures of smoking revealed significant inverse associations with PD (P<.05) and trends in odds ratios (P<.005). Increasing intensity of coffee drinking was inversely associated with PD (test for trend P = .05). Increasing dosage (trend P = .009) and intensity (trend P = .01) of total caffeine consumption were also inversely associated, with high dosage presenting a significant inverse association for PD (odds ratio = 0.58; 95% confidence interval, 0.34-0.99). There were no significant associations between nonsteroidal anti-inflammatory drugs and PD.<br><br>Conclusions Inverse associations of smoking and caffeine were corroborated using families with PD, thus emphasizing smoking and caffeine as important covariates to consider in genetic studies of PD.<br><br>Cigarette smoking, caffeine, and nonsteroidal anti-inflammatory drugs (NSAIDs) are reported protective factors for Parkinson disease (PD), but few family-based studies have examined these associations. Numerous studies have described associations for smoking and caffeine with meta-analysis indicating that smokers and caffeine consumers are significantly less likely to develop PD than those never exposed.1 Initial studies of NSAIDs have proposed that this exposure may also delay or prevent the onset of PD.2,3<br><br>Family-based case-control data sets are commonly used for genetic association studies, as this study design is robust to confounding by ethnic background (ie, population stratification). Cases and family controls are generally well matched on unmeasured genetic and environmental factors that may predispose to exposure behaviors and to disease. Examination of environmental associations in family-based samples thus reduces confounding by familial influences on exposure. We analyzed a family-based case-control data set for associations between PD and 3 factors inversely associated with PD in prior studies: smoking, caffeine, and NSAIDs.
