ESPEYB21 3. Thyroid Thyroid Cancer (1 abstracts)
3.14. Polygenic risk scores, radiation treatment exposures and subsequent cancer risk in childhood cancer survivors
Todd M Gibson , Danielle M Karyadi , Stephen W Hartley , Michael A Arnold , Amy Berrington de Gonzalez , Miriam R Conces , Rebecca M Howell , Vidushi Kapoor , Wendy M Leisenring , Joseph P Neglia , Joshua N Sampson , Lucie M Turcotte , Stephen J Chanock , Gregory T Armstrong & Lindsay M Morton
Nat Med. 2024 Mar;30(3):690-698. doi: 10.1038/s41591-024-02837-7. PMID: 38454124
Brief Summary: This study explored the combined effect of genetic predisposition and radiation exposure on the risk of developing subsequent cancers in survivors of childhood cancer. It included genotype data from 11,220 5-year survivors and focused on six subsequent cancer types: basal cell carcinoma (BCC), breast cancer, thyroid cancer, squamous cell carcinoma (SCC), melanoma, and colorectal cancer. Polygenic risk scores (PRS) were derived from genome-wide association studies (GWAS) in the general population and were applied to the survivors to assess their predictive value in this unique population. PRS were associated with the risk of subsequent cancers, particularly BCC (odds ratio per s.d. of the PRS: OR =1.37, 95% confidence interval (CI) =1.29–1.46), breast cancer (OR =1.42, 95% CI =1.27–1.58), thyroid cancer (OR =1.48, 95% CI =1.31–1.67), and melanoma (OR =1.60, 95% CI =1.31–1.96).
An important finding is that the joint effects of radiation exposure and PRS are more than additive. therefore, survivors with both high radiation exposure and high PRS have a particularly elevated risk of developing these cancers. For example, the cumulative incidence of subsequent thyroid cancer by age 50 was 18% for those exposed to high neck radiation (10-30 Gy) and with a high PRS, compared to 6% for those with similar radiation exposure but a low PRS.
Integrating genetics with treatment history may provide valuable insights for risk stratification in childhood cancer survivors, particularly those at higher risk due to radiation exposure. These findings could influence long-term follow-up guidelines and cancer surveillance strategies in this population.
Currently, the recommendation for thyroid cancer surveillance in survivors of childhood, adolescent, and young adult (CAYA) cancer are counseling regarding risk and surveillance options for differentiated thyroid carcinoma, at least every 5 years. If the decision to commence surveillance is made, a shared decision should be made for one of these two surveillance modalities:
- neck palpation, every 1 to 2 years, starting 5 years after radiotherapy, or- thyroid ultrasonography, every 3 to 5 years, starting 5 years after radiotherapy [1].
If genotyping and PRS calculation become regular care, an interesting question is whether and how this will change current thyroid cancer surveillance in CAYA cancer survivors: more intensive in those with a higher risk, or less intensive in those with a lower risk?
Reference: 1. Laura van Iersel, Renee L Mulder, Christian Denzer, et al. Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors. Endocr Rev. 2022 Sep 26;43(5):794-823. doi: 10.1210/endrev/bnab040. PMID: 34962573
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ESPE Yearbook of Paediatric Endocrinology
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