BP.04.02] TUMOR NECROSIS FACTOR-RELATED APOPTOSIS-INDUCING LIGAND (TRAIL) IS ASSOCIATED WITH INFLAMMATION IN YOUNG ADULT SURVIVORS OF CHILDHOOD CANCER

Abstract

Objective: Cancer survivors previously treated with cardiotoxic therapies (anthracycline, chest and neck radiotherapy) are at risk for early atherosclerosis secondary to inflammation and endothelial dysfunction. The aim of the study was to assess markers of inflammation and subclinical atherosclerosis in young adult survivors of childhood cancer. Design and method: We evaluated cardiovascular risk factors and assessed biochemical markers of inflammation and intima-media thickness (IMT) in 50 five-year survivors of childhood cancer (CCS) and in 29 healthy controls. Results: Cancer survivors (age 23.6 ± 2.8 years, 10.4 ± 4.1 years since the end of treatment, 94% with hematologic malignancies) had higher total cholesterol level (4.7 ± 1 versus 4.3 ± 0.6 mmol/l; p = 0.03) and LDL cholesterol (2.6 ± 0.9 versus 2.2 ± 0.6 mmol/l; p = 0.03) but were comparable with controls for other traditional cardiovascular risk factors. IMT was similar in both groups (0.43 ± 0.05 mm in CCS and 0.41 ± 0.05 mm in controls; p = 0.13). Inflammatory markers: hsCRP and fibrinogen were increased in CCS compared to controls (0.79 [0.33–2.42] versus 0.30 [0.17–0.57] mg/l; p = 0.006 and 2.8 [2.5–3.3] versus 2.2 [1.9–2.4] g/l; p < 0.001, respectively). Serum TRAIL levels were lower in CCS than in controls (97.6 ± 38.7 versus 127.8 ± 37.6 pg/ml; p = 0.001) and correlated negatively with PTX3 (r = −0.64; p < 0.001). IMT was not associated with inflammatory markers in CCS. Conclusions: Young childhood cancer survivors 10 years after treatment had increased cholesterol level and inflammatory markers but no signs of subclinical atherosclerosis. Low serum TRAIL levels were significantly associated with higher PTX3. It may suggest possible role of TRAIL in the control of chronic inflammatory activation and reflect a dysregulation of apoptosis in patients previously treated for cancer. (The study was supported by the Research Grant No. DEC-2012/7/N/NZ5/0080.)