For Childhood Cancer Survivors, Genetics Influence Risk of Cancer Later in Life

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Common inherited genetic factors that predict cancer risk in the general population may also predict elevated risk of new cancers among childhood cancer survivors, according to a recent NCI study. The findings, published in Nature Medicine, provide additional evidence that genetics may play an important role in the development of subsequent cancers in survivors of childhood cancer.

Childhood cancer survivors are known to have a higher risk of developing a new cancer later in life due to adverse effects of cancer treatment or rare inherited genetic factors. In the new study, researchers evaluated the combined effect of common variants with history of radiation treatment and found the resulting elevated cancer risk was greater than the sum of the individual associations for treatment and genetic factors alone.

Researchers used data from genome-wide association studies (GWAS), conducted in large populations of healthy individuals. They bundled the effects of the large numbers of variants from GWAS into polygenic risk scores. These scores have shown promise for predicting cancer risk in the general population, but it has not been shown whether they are associated with the risk of subsequent cancer among childhood cancer survivors.

The researchers looked at the association between polygenic risk scores and risk of basal cell carcinoma, female breast cancer, thyroid cancer, squamous cell carcinoma, melanoma and colorectal cancer among 11,220 childhood cancer survivors from two large cohort studies. 

For all of these cancers except colorectal cancer, the polygenic risk scores in the general population were associated with the risk of these same cancers among childhood cancer survivors.

Moreover, by age 50, survivors with higher polygenic risk scores and higher radiation exposure had a greater cumulative incidence of basal cell carcinoma, breast cancer or thyroid cancer.

Polygenic risk scores are not yet used routinely in the clinic.

Lead investigator Dr. Todd M. Gibson of NCI’s Division of Cancer Epidemiology and Genetics said, “The hope would be that…we can incorporate genetics along with treatment exposures and other risk factors to provide a more complete picture of a survivor’s risk of subsequent cancers to help guide their long-term follow-up care.”