Combined Effects of Smoking, Coffee, and NSAIDs on Parkinson’s Disease Risk Karen M. Powers, BS, 1 Denise M. Kay, PhD, 2 Stewart A. Factor, DO, 3,4 Cyrus P. Zabetian MD, MS, 5,6 Donald S. Higgins, MD, 4 Ali Samii, MD, 6,7 John G. Nutt, MD, 8 Alida Griffith, MD, 9 Berta Leis, PhD, 9 John W. Roberts, MD, 10 Erica D. Martinez, BS, 5,6 Jennifer S. Montimurro, BS, 2 Harvey Checkoway, PhD, 1 and Haydeh Payami, PhD 2 * 1 Department of Environmental and Occupational Health Sciences, School of Public Health and Community Medicine, University of Washington, Seattle, Washington 2 Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, New York 3 Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 4 Parkinson’s Disease and Movement Disorder Center, Albany Medical Center, Albany, New York 5 Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 6 Department of Neurology, University of Washington School of Medicine, Seattle, Washington 7 Parkinson’s Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington 8 Department of Neurology, Oregon Health and Science University, Portland, Oregon 9 Booth Gardner Parkinson’s Care Center, Evergreen Hospital Medical Center, Kirkland, Washington 10 Virginia Mason Medical Center, Seattle, Washington Abstract: Inverse associations of Parkinson’s disease (PD) with cigarette smoking, coffee drinking, and nonsteroidal anti- inflammatory drug (NSAID) use have been reported individu- ally, but their joint effects have not been examined. To quantify associations with PD for the individual, two-way and three-way combinations of these factors, a case– control association study with 1,186 PD patients and 928 controls was conducted. The study setting was the NeuroGenetics Research Consortium. Subjects completed a structured questionnaire regarding smok- ing, coffee, and NSAID consumption. Odds ratios were calcu- lated using unconditional logistic regression. Smoking, coffee, and over the counter NSAID use as individual factors exhibited significantly reduced risks of 20% to 30%. The two-way and three-way combinations were associated with risk reduction of 37% to 49%, and 62%, respectively. Smoking and coffee exhibited significant inverse risk trends with increasing cumu- lative exposures, suggesting dose–response relations. With re- spect to the combination of all three exposures, persons who were at the highest exposure strata for smoking and coffee and used NSAIDs had an estimated 87% reduction in risk (OR = 0.13, 95% CI = 0.06 – 0.29). Whether this finding reflects true biologic protection needs to be investigated. © 2007 Movement Disorder Society Key words: Parkinson’s disease; smoking; coffee; NSAIDs; nonsteroidal anti-inflammatory drugs Reduced Parkinson’s disease (PD) risk among ciga- rette smokers, with strong evidence for inverse dose– response gradients, has been demonstrated consistently. 1 Inverse associations with PD risk have also been ob- served for caffeine intake, albeit not as consistently as with smoking. 1-4 Results of associations for nonsteroidal anti-inflammatory drugs (NSAIDs) and PD have been mixed, with some studies suggesting a reduced risk and others finding no association. 5-8 The combined effects of smoking, coffee drinking and NSAIDs have not been reported previously. Here we present findings from a case– control study on the individual and combined ef- fects of smoking, coffee, and NSAIDs on PD risk. *Correspondence to: Haydeh Payami, Genomics Institute, Wads- worth Center, New York State Department of Health, PO Box 22002 Albany, NY 12201-2002. E-mail: hpayami@wadsworth.org Received 14 June 2007; Revised 18 September 2007; Accepted 21 September 2007 Published online 6 November 2007 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.21782 Movement Disorders Vol. 23, No. 1, 2008, pp. 88-95 © 2007 Movement Disorder Society 88