Parkinson's disease, smoking, and family history

There is growing evidence that both genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). The hypothesis of an in teraction between genetic and environmental risk factors has been little ex plored, and never using a population-based case-control study design. Our o bjective was to investigate the possible interaction between smoking and fa mily history in the etiology of PD, as part of a collaborative population-b ased case-control study. We included 149 nondemented PD patients ascertaine d in three European prevalence surveys using a two-phase design. Each patie nt was matched by age (+/-2 years), gender, and center to three controls dr awn from the same populations (n=375). Presence of PD among first-degree re latives and smoking history were assessed through an interview for 127 case s and 306 controls. In the overall sample we found suggestive evidence that family history and ever-smoking interact in determining the risk of PD (P= 0.09), with individuals exposed to both risk factors having the highest ris k (OR=10.0; 95 % CI=2.0-49.6). Analyses were repeated after stratification into two age-groups (cutoff: 75 years). In older patients, the joint exposu re to both risk factors was associated with a significant increase in the r isk of PD (OR=17.6; 95 % CI=1.9-160.5). Among younger subjects, the OR for joint exposure was not significant. In conclusion, our findings suggest tha t smoking and family history interact synergistically on a multiplicative s cale in determining the risk of PD in individuals older than 75 years.