Genetic Factors Influence Subsequent Cancer Risk in Childhood Cancer Survivors

MONDAY, March 18, 2024 (HealthDay News) -- Polygenic risk scores (PRSs) derived from the general population are associated with a subsequent risk for certain cancers among survivors of childhood cancer, with an additive risk for PRS and radiotherapy, according to a study published online March 7 in Nature Medicine.

Todd M. Gibson, Ph.D., from the National Cancer Institute in Bethesda, Maryland, and colleagues examined the impact of genetic predisposition on the risk for subsequent cancers among survivors of childhood cancer. Genotype data were combined for 11,220 five-year survivors from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort.

The researchers found that cancer-specific PRSs derived from the general population, genome-wide association study, cancer loci identified survivors of European ancestry at an increased risk for subsequent basal cell carcinoma, female breast cancer, thyroid cancer, squamous cell carcinoma, and melanoma; the association for colorectal cancer was not significant. More than additive increases in the risk for basal cell carcinoma and breast and thyroid cancers were seen in an examination of joint associations between PRSs and radiotherapy. The cumulative incidence of subsequent cancer by age 50 years was increased for those with high versus low PRS among survivors with radiotherapy exposure.

"These findings suggest the potential utility of PRSs for enhancing risk stratification and refining follow-up guidelines related to subsequent cancers, particularly in survivors already at increased risk because of their history of radiotherapy," the authors write.

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