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Family history of melanoma and Parkinson disease risk

From the Channing Laboratory (X.G., J.H., A.A.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Departments of Nutrition (X.G., K.C.S., A.A.) and Epidemiology (A.A.), Harvard University School of Public Health, Boston, MA; and Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston.

Address correspondence and reprint requests to Dr. Xiang Gao, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave., Boston, MA 02115 xiang.gao{at}channing.harvard.edu.

Background: Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD.

Methods: We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study. Information on family history of melanoma in parents or siblings was assessed via questionnaire. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards models and pooled using a fixed-effects model.

Results: During 14–20 years follow-up, we identified 616 incident PD cases. A family history of melanoma in a first-degree relative was associated with a higher risk of PD (multivariate relative risk = 1.85; 95% confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking, ethnicity, caffeine intake, and other covariates. In contrast, we did not observe significant associations between a family history of colorectal, lung, prostate, or breast cancer and PD risk. Interactions between melanoma family history and age, smoking, or caffeine intake were not significant and subgroup analyses according to these factors generated similar results.

Conclusions: Our findings support the notion that melanoma and Parkinson disease (PD) share common genetic components. The genetic determinants of melanoma could therefore be explored as susceptibility candidate genes for PD.

Abbreviations: BMI = body mass index; CDK = cyclin dependent kinase; CI = confidence interval; HPFS = Health Professional Follow-up Study; NHS = Nurses' Health Study; OR = odds ratio; PD = Parkinson disease; RR = relative risk; SER = standardized event ratio.

Supplemental data at www.neurology.org.

The study was supported by NIH/NINDS grant R01 NS048517, and the Parkinson Study Group and the Parkinson's Disease Foundation's Advancing Parkinson's Treatments Innovations Grant.

Disclosure: Author disclosures are provided at the end of the article.

Received April 14, 2009. Accepted in final form July 22, 2009.