Telomere Length-Associated Genetic Variants and the Risk of Thyroid Cancer in Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study (CCSS)

Background: Given the inverse relationship previously described between telomere content and thyroid subsequent malignant neoplasm (thyroid SMN) in survivors of childhood cancer, we investigated the relationship between known genetic determinants of leukocyte telomere length and thyroid SMN among survivors. Methods: Leveraging data from a large, genotyped survivor cohort, the Childhood Cancer Survivor Study, we used a well-described genetic risk score method to estimate the hazard ratio for thyroid SMN among 5,324 genotyped survivors. Results: We identified 118 survivors with thyroid SMN and 5,206 without thyroid SMN. No association between genetically-estimated leukocyte telomere length and risk for thyroid SMN was identified. Conclusions: Our results suggest that variation in common SNPs influencing leukocyte telomere length is not strongly associated with risk for thyroid SMN in survivors of childhood cancer. Impact: The previously-observed inverse relationship between leukocyte telomere length and thyroid SMN risk in survivors of childhood cancer may be related to alternative molecular mechanisms, and warrants further study.