Cigarette smoking and Parkinson’s disease: a case-control study in a population characterized by high prevalence of pesticide exposure.
Galanaud JP, Elbaz A, Clavel J, Vidal J-S, Correze J-R, Alperovitch A, et al.;
Commented by , 21 Apr 2005
In this commentary, Professor Emre comments on two articles on the same topic. One is mentioned in the headline, and the other is the following:
Family-based case-control study of cigarette smoking and Parkinson disease
Scott WK, Zhang F, Stajich JM, Scott BL, Stacy MA, Vance JM.
Neurology 2005; 64 (3); 442-447
Background
An inverse relation has been reported between cigarette smoking and risk of Parkinson’s disease. Two recent studies in two special populations confirm and extend these findings.
Aim of the studies
The objective of the first study (Galanaud et al.) was to study the relationship between cigarette smoking and PD in a population characterized by a high prevalence of pesticide exposure. This was relevant because exposure to pesticides was hypothesized to increase risk of PD.
The aim of the second study (Scott et al.) was to determine whether patients with PD are less likely to report a history of cigarette smoking than their unaffected siblings.
Methods
The first was a case-control study conducted among workers connected to professional agricultural work. A total of 247 cases and 676 controls matched on age, sex and region of residency were included. Data on smoking was obtained through in-person interviews, pesticide exposure was assessed using a case-by-case expert evaluation procedure.
The second study was a matched case-control study of 140 sibships whereby 143 PD patients were compared to 168 sibling controls. Cigarette smoking story was collected by telephone inteviews, conditional logistic regression was used to examine the relationship between smoking and PD, confounding by age and sex was controlled for.
Results
In the first study an inverse relationship between ever cigarette smoking and PD was found (odds ratio= 0.6; 95% confidence interval= 0.4-0.9), the strength of the association increased with the number of pack-years. The inverse association was also present among subjects professionally exposed to pesticides (odds ratio=0.5, confidence interval=0.3-0.8) and was independent of the duration of exposure among men.
The authors concluded that the inverse association between cigarette smoking and PD was confirmed in a population characterized by a high prevalence of professional pesticide exposure, and that this association was not significantly modified or confounded by exposure to pesticides.
The second study revealed that ever smoking, current smoking, longer duration (in years), dose (in packs/ day) and intensity (in pack-years) of smoking were singificantly and inversely associated with PD (p<0.05). There was no influence of sex, age at onset, or recency of exposure.
The authors concluded that individuals with PD are significantly less likely to have smoked regularly than their unaffected siblings. They pointed out that this association was detected even though discordant sibling pairs are more likely to be overmatched for environmental exposures than unmatched case and control groups.
Professor Emre’s comments
The inverse relation betwen cigarette smoking and the risk of PD is one of the most robust epidemiological associations known for PD. Numerous retrospective case-control and cohort studies as well as prospective studies in various populations demonstrated this association, a recent meta-analysis of these studies revealed that patient with PD are half as likely to report ever having smoked cigarettes as compared to those unaffected by PD (ref. 1).
The mechanisms of this apparent protection have been disputed, a protective role of nicotine was suggested, either by reduction of monoamine oxidase activity, which in turn might be neuroprotective or through a direct neuroprotective effect of nicotine (ref. 2; ref. 3).
Alternatively recall bias, confounding, a premorbid personality trait with an aversion against smoking have been proposed (ref. 4). These two studies further confirm and extend this association. In the first study patients with high exposure to pesticides and thus theoretically at increased risk to develop PD also seemed to demonsrate the inverse association. In other words if smoking is indeed protective it seemed to do so also in this high risk population.
The second study is also important because it is a family-based case control study which took the siblings of patients as controls, thus reducing the effect of confounding due to potential ethnic variability and resulting genetic variation in control groups.
In this setting true disease related differences between affected and unaffected siblings are expected to be more apparent against a common background. Family-based studies are commonly used to study genetic factors, this is a good example that they can be utilized to study environmental factors.
In conclusion the inverse association between cigarette smoking and the risk of PD has been confirmed with two further studies with novel populations, but the mystery as to the mechanism further remains.
References
1. Hernan MA, Takkouche B, Caamano-Isorna F and Gestal-Otero JJ. A meta-analysis of coffee drinking, cigarette smoking, and the risk of Parkinson's disease. Annals of Neurology 2002; 52; 276-284
2. Tanner CM, Goldman SM, Aston DA, et al. Smoking and Parkinson's disease in twins. Neurology 2002; 55; 1350-1358
3. Castagnoli K and Murugesan T. Tobacco leaf, smoke and smoking, MAO inhibitors, Parkinson's disease and neuroprotection; are there links? Neurotoxicity 2004; 25; 279-291
4. Morens DM, Grandinetti A, Reed D, White LR and Ross GW. Cigarette smoking and protection from Parkinson’s disease: false association or etiologic clue? Neurology 1995; 45; 1041-1051