Objective: To study the association between polymorphisms associated with the risk of Parkinson’s disease (PD) and several types of cancer.

Background: The relationship between PD and cancer is complex. While the risk of cancer, in particular smoking-related cancers, is generally reduced in Parkinson’s patients, due to a lower frequency of smoking in cases than controls, there is an increased risk of specific cancers such as melanoma or breast cancer in some studies. The origin of these associations is not well known but could be partly genetic.

Method: We investigated the association between a polygenic risk score (PRS) of PD (1) based on 44 polymorphisms and four cancers: breast, melanoma, prostate, ovarian. We used summary statistics from a genome-wide association study (GWAS) of the Melanoma Meta-analysis Consortium (11,523 cases, 20,860 controls) to test for the association between PRS and melanoma. For other cancers, we used publicly available GWAS summary statistics from the Breast Cancer Association Consortium (BCAC – 62,533 cases, 60,976 controls), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL – 79,148 cases, 61,106 controls), and Ovarian Cancer Association Consortium (OCAC – 10,157 cases, 13,904 controls). For analyses based on summary statistics, the associations of the PRS with cancer were estimated using the R package gtx (2).

Results: The PRS showed significant associations with two cancers out of four. An increasing number of PD risk alleles was associated with a higher risk of breast cancer (OR=1.06 [1.03-1.09]) and lower risk of ovarian cancer (OR=0.95 [0.91-0.99]). There were no significant associations for the other cancer types.

Conclusion: These results suggest that PD susceptibility polymorphisms may display pleiotropic effects for breast and ovarian cancer. Further analyses are needed in order to provide insight into common mechanisms underlying these diseases, including LD score regression, to estimate the genetic correlation between PD and these cancers, and cross-phenotype meta-analysis to leverage pleiotropic polymophisms.These analyses are currently underway using GWAS data from the COURAGE-PD study (15,500 cases, 11,500 controls).

References: [1] Chang D, Nalls MA, Hallgrímsdottir IB, Hunkapiller J, Van Der Brug M, Cai F, et al. A meta-analysis of genome-wide association studies identifies 17 new Parkinson’s disease risk loci. Nat Genet. 2017; [2] Dastani Z, Hivert MF, Timpson N, Perry JRB, Yuan X, Scott RA, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: A multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8(3).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-the-role-of-known-susceptibility-genes-of-parkinsons-disease-in-cancer/