Genetic Effect of Chemotherapy Exposure in Children of Testicular Cancer Survivors

Purpose: Cancer survivors express anxiety that chemotherapy exposure may lead to transmissible genetic damage in posttreatment children. Preclinical models suggest that chemotherapy exposure may result in considerable genomic alterations in postexposure progeny. Epidemiologic studies have not demonstrated a significant increase in congenital abnormalities in posttreatment children of cancer survivors, but the inherited genome-wide effect of chemotherapy exposure in humans is unknown. Experimental Design: Two testicular cancer survivors cured with chemotherapy who had children pre- and postexposure without sperm banking were identified. Familial germline whole genome sequencing (WGS) was performed for these families, and analytic methods were utilized to identify de novo alterations, including mutations, recombinations, and structural rearrangements in the pre- and postexposure offspring. Results: No increase in de novo germline mutations in postexposure children compared with their preexposure siblings was found. Furthermore, there were no increased short insertion/deletions, recombination frequency, or structural rearrangements in these postexposure children. Conclusions: In two families of male cancer survivors, there was no transmissible genomic impact of significant mutagenic exposure in postexposure children. This study may provide possible reassuring evidence for patients undergoing chemotherapy who are unable to have pretreatment sperm cryopreservation. Expanded cohorts that utilize WGS to identify environmental exposure effects on the inherited genome may inform the generalizability of these results. Clin Cancer Res; 22(9); 2183–9. ©2015 AACR.