Sperm DNA Integrity in Men Treated for Childhood Cancer

Purpose: It is not known whether childhood cancer and its treatment are associated with sperm DNA damage, which subsequently affects fertility and might be transmitted to the offspring. The aim of this study is to assess DNA fragmentation index (DFI) as an indicator of sperm DNA integrity in childhood cancer survivors (CCS), with treatment regimen taken into account. Experimental Design: In 99 CCS and 193 age-matched healthy controls, DFI was assessed by using sperm chromatin structure assay. Results: In the whole group of CCS, DFI was increased compared with the controls, with borderline statistical significance [mean difference, 1.8%; 95% confidence interval (95% CI), −0.0088%-3.7%]. Those treated with radiotherapy only (mean difference, 6.0%; 95% CI, 1.6–10%) or surgery only (mean difference, 2.9%; 95% CI, 0.083–5.8%) had statistically significantly higher DFI than the controls. The odds ratio (OR) for having DFI >20%, which is associated with reduced fertility, was significantly increased in CCS compared with the control group (OR, 2.2; 95% CI, 1.1–4.4). For the radiotherapy-only group, the OR was even higher (OR, 4.9; 95% CI, 1.3–18). DFI was not associated with dose of scattered testicular irradiation or type of chemotherapy given. Conclusions: DFI was increased in CCS, with those treated with chemotherapy being the only exception. This sperm DNA impairment may be associated with the disease per se rather than due to the treatment, and may have negative consequences in terms of fertility and risk of transmission to the offspring. Clin Cancer Res; 16(15); 3843–50. ©2010 AACR.