The number of childhood cancer survivors in the United States is growing, with an overall survival rate of more than 85 per cent five years following diagnosis.
Survivors, however, may still be at higher risk of a variety of health issues, including second malignancies.
Using data from the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (St Jude Life), researchers at St. Jude Children’s Research Hospital discovered a genetic explanation for why a small percentage of survivors are more likely to develop second cancers, which may be more severe or fatal.
The findings, which will help with genetic counselling, testing, and the implementation of personalised cancer screening and preventive programmes, were published in The Lancet Oncology.
The St Jude group showed that survivors with pathogenic (damaging) genetic variants in specific genes, called cancer-predisposing variants, are at an increased risk of developing second, or subsequent, cancers as adults, and those cancers are more likely to be severe and deadly.
The scientists had previously identified that survivors with pathogenic variants in one of 60 different cancer-predisposing genes or 127 DNA damage repair genes were more likely to experience a second or subsequent cancer.
This study extends that research to show a direct connection between cancer-predisposing variants and increased second-cancer-related mortality. Many of these genetic variants are known to be causally linked to cancers. For example, the tumor suppressor gene TP53 is one of the 60 genes included in the analysis.