Increased Risk of Cancer in Men with Peyronie's Disease
Men with Peyronie&[prime]s Disease (PD) may have increased prevalent comorbidities, including malignancy. Here we examine the relationship between PD and malignancy using clinical and genetic data.
We analyzed data from the Truven Health MarketScan claims database from 2007-2013. Men with PD were compared to men matched for age and duration of follow-up with erectile dysfunction (ED) and controls. The incidence of 18 categories of malignancy was compared among each group utilizing a Cox regression model. A father and son with both PD and Dupuytren&[prime]s disease (DD), a related fibrotic diathesis, were whole exome sequenced (WES), and shared non-synonymous single nucleotide polymorphisms (SNPs), which were analyzed for association with malignancy, and cross-referenced against gene expression data from The Cancer Genome Atlas (TCGA).
In all, 48,423 men with PD, 1,177,428 men with ED, and 484,230 controls were identified. The mean age among all three cohorts was ~49 years old, and mean follow-up time was ~4.4 years. Compared to controls, men with PD had an increased risk of stomach (HR, 95% CI; 1.43, 1.06-1.14) testis cancer (1.39, 1.05-1.84), and melanoma (1.19, 1.02-1.38). When compared to men with ED, men with PD had an increased risk of developing prostate cancer (1.38, 1.28-1.49). Analysis of WES data identified 150 shared, potentially deleterious nonsynonymous SNPs between father and son, with alterations in genes involved in genitourinary and gastrointestinal cancers. Using TCGA, expression data demonstrated primarily suppression of tumor suppressor gene expression in genes overlapping with altered genes shared between father and son.
Men with PD are at increased risk for numerous malignancies compared to age matched men with ED and controls. Genetic alterations in men with both PD and DD independently support a risk for genitourinary and gastrointestinal cancers. These findings suggest that men with PD should be closely monitored after diagnosis (and treatment) of their PD.
Funding: This work is also supported in part by the Notsew Orm Sands Research Foundation (to AWP).