Cardiovascular Morbidity in Testicular Cancer Survivors: Study of Risk Factors and Assessment of Pharmacogenomic Determinants of Toxicity

BACKGROUND: Evidence has emerged that patients cured with cisplatin-bleomycin chemotherapy from disseminated testicular cancer (TC) develop a large number of cardiovascular risk factors (CRF) several years later. Recently, we observed an increased incidence of cardiac events 10-20 years after chemotherapy, possibly as a result of increased occurrence of CRF. Additional cardiovascular damage was observed after treatment: disturbed diastolic function of the left ventricle, microalbuminuria and increased endothelial damage parameters. Furthermore, a metabolic syndrome (syndrome X) with insulin-resistance, dyslipidemia, hypertension and endothelial damage was found in about one third of our cured patients. The investigators hypothesize that endothelial damage and metabolic changes caused by the bleomycin and cisplatin chemotherapy are the main causes for the observed increase in cardiovascular disease in these young cancer survivors. Genetic susceptibility may be an important determinant of individual risk of toxicity in individual patients. PURPOSE: 1. To identify risk factors for cardiovascular disease (CVD) following testicular cancer. 2. To obtain insight into the pathway(s) of CVD development, by examining whether clinical CVD following testicular cancer is associated with a preceding unfavorable cardiovascular risk factor profile and/or with treatment-related factors. 3. To investigate genetic polymorphisms in pathogenetically important pathways that are potentially involved in the development of treatment related cardiovascular morbidity following testicular cancer. PATIENTS AND METHODS: Patients with non-seminomatous testicular cancer who have been uniformly treated with orchidectomy and cisplatin-bleomycin combination chemotherapy at the University Hospital Groningen, The Netherlands, since 1977 but before 2000 are eligible. 380 patients with non-seminomatous testicular cancer fulfill these criteria. A close routine follow-up of these patients after treatm