Parkinson's Disease: A Protective Effect of Smoking?
Initial Award Abstract
Parkinson's disease (PD) is one of a few conditions in which cigarette smoking appears to decrease the risk of developing the disease, with a reduced risk of 50% among ever smokers compared to never smokers. Despite the fact that this reduced risk among cigarette smokers has been consistently observed in studies conducted over the past several decades, there has been very little epidemiologic research to investigate the possible explanations for this apparent protective effect. Although it is possible that a chemical or biological effect of cigarette smoke provides protection against the development of PD, alternative explanations are also plausible. One theory suggests that the effect of smoking is due to another factor, such as personality type or the genetic tendency to take up addictive behaviors, which explain both the decreased likelihood of taking up the smoking habit and the risk of developing PD in later life.
We propose to conduct a study of PD patients and normal controls (also called a case-control study) to evaluate genetic, environmental and behavioral factors that may explain this apparent protective effect of smoking in PD. We hypothesize that genetic variants associated with the propensity to engage in addictive behaviors may be less frequent among PD cases than controls, especially since some of these genetic variants alter dopaminergic transmission in the brain (dopamine is the brain chemical that is depleted in PD). We will also assess whether nonsmokers who are exposed to environmental tobacco smoke from the smoking habits of others may be at reduced risk of developing PD. If environmental (or passive) smoke exposure is also more frequent among PD patients than controls, this would suggest that a chemical effect of both mainstream and sidestream tobacco smoke has a direct biological effect that reduces the risk of developing PD. We also plan to gather data from cigarette smokers regarding the perceived strength of their addiction, and more detailed information regarding their lifetime history of alcohol consumption, another factor that has been associated in recent studies with a reduced risk of developing PD.
This study will use blood samples and risk factor data obtained from PD cases and controls in a recently completed case-control study conducted within the Northern California Kaiser Permanente Medical Care Program. A lifetime history of cigarette smoking has already been obtained for the study subjects, which include 509 newly diagnosed PD cases and 541 age- and gender-matched controls. Additional information will be sought from all study subjects using a telephone-administered structured interview and will include questions regarding: exposure to passive smoke, an assessment of the addictive potential of cigarette smoke among former and current smokers, a measure of premorbid personality, and a lifetime history of alcohol consumption. By combining laboratory-based investigation of these addiction susceptibility genes with detailed information regarding cigarette smoking and other addictive behaviors, we hope to gain insight regarding the nature of the inverse associations of cigarette smoking and other addictive behaviors with Parkinson's disease that can provide information for future research on the causes of Parkinson's disease. |