Change in telomere length and cardiovascular risk in testicular cancer survivors.

Abstract

12079 Background: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular events, as part of an early aging phenotype. Telomere shortening could be a mechanism contributing to these events and their risk factors. Methods: In a prospectively followed cohort of patients with disseminated TC who received cisplatin containing CT (Lubberts et al., Eur J Cancer 2016), mean absolute leukocyte telomere length (TL) was measured using qPCR before and one year after start of cisplatin containing CT. Cardiovascular risk factors, including development of the metabolic syndrome (according to the NCEP ATP III definition) and hypogonadism (LH >10 U/L or testosterone < 10 nmol/L or use of testosterone suppletion), were assessed before and up to 5 years after CT. Shortening of TL was defined as a decrease of >33% after one year compared to baseline; short TL was defined as <5 kilobase (kb) pair (=P25). Data are presented as median (range). For comparisons, a Mann-Whitney U or Chi-Square test was applied. Results: 55 out of 73 patients of the initial cohort were evaluable for this analysis. CT regimens consisted of 3xBEP (n=41), 4x BEP (n=11), 4xEP (n=3). At baseline, patients with a BMI > 30 kg/m2 (n=12) had a shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), p=.045); there was no difference in age. For the whole group, TL did not change one year after CT compared to baseline (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), p=.335). Patients with TL shortening after 1 year (n=7) showed a significant increase in diastolic blood pressure (p=.007) and triglycerides (p=.003), compared to those with unchanged TL (table). TL shortening after 1 year or short TL at baseline (n=7+11) are not significant predictors for newly developed metabolic syndrome (25 vs. 21%; p=.777), nor hypogonadism (38 vs. 17%; p=.120) after 5 years, compared to the others. Conclusions: A small subset of TC patients treated with cisplatin containing CT showed shortening of TL 1 year after treatment. This shortening is associated with a rise in diastolic blood pressure and triglycerides. Short or shortening of telomeres are not predictive for development of the metabolic syndrome or hypogonadism. [Table: see text]