Hemochromatosis gene (HFE) mutations and chemotherapy-related cardiovascular risk profile in testicular cancer survivors (TCS)
14589 Background: TCS show an increased incidence of treatment-related cardiovascular disease. Standard chemotherapy (CT) may cause tissue damage by inducing free oxygen radicals through release of redox-active iron from body iron stores. HFE mutations associated with altered body iron load may therefore contribute to an increase in CT-induced free oxygen radicals and tissue damage. We investigated whether two HFE mutations (C282Y and H63D) are associated with cardiovascular risk profile in TCS. Methods: From a group of 90 TCS with a known cardiovascular status (JCO 2005; 23: 3718–25), genomic DNA for genotyping was available for 63 TCS (median (range) age at follow-up 35 y (24–54) and median follow-up duration 7 y (3–13)). Two HFE genotype groups were composed: HFE mutation (mut) (n = 19; any mutation C282Y and/or H63D) and HFE wild type (wt) (n = 44). Both groups were compared for cardiovascular risk profile, using Mann-Whitney U Test or Fisher’s Exact Test. Results: Groups had received comparable CT regimens. Body iron stores as reflected by plasma ferritin and transferrin saturation were not different for the HFE mut vs HFE wt group, respectively 104 μg/l (21–413) vs. 90 μg/l (22–569); p = 0.53 and 31% (20–49) vs. 30% (11–59); p = 0.15. Signs of vascular damage estimated by urinary albumin excretion and Von Willebrand factor levels were not significantly different: respectively 8.3 mg/24 h (4–165) vs. 7.7 mg/24 h (3–647); p = 0.90 and 90% (52–296) vs. 102% (28–235); p = 0.25. The prevalence of cardiovascular risk factors obesity (BMI > 27.8 kg/m2), metabolic syndrome (NCEP ATP III-criteria) and hypertension (mean 24-h blood pressure >135/85 mmHg) are shown in the table. Conclusion: TCS with a mutation in the HFE gene do not show more signs of cardiovascular damage after CT compared to TCS with wt HFE. However, the data suggest that TCS with a HFE mutation may have more frequently cardiovascular risk factors. Further study in a larger group of TCS is needed to explore this observation. [Table: see text] No significant financial relationships to disclose.