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Washington, October 8: The number of childhood cancer survivors is increasing in the United States, with an overall survival rate of more than 85% five years after diagnosis. However, survivors may still be more vulnerable to many diseases, such as a second cancer.
Researchers at St. Jude Children’s Research Hospital, using data from the Childhood Cancer Survivor Study (CCSS) and St. It is possible Jude Lifetime Cohort Study (St. Jude Life).
The findings, which will help in the implementation of genetic counselling, testing and personalized cancer screening and preventive programs, were published in The Lancet Oncology.
The St. Jude group showed that pathogenic (harmful) genetic variants in specific genes, called cancer-predisposing variants, increase the risk of survivors developing a second or subsequent cancer as adults, and those with those cancers. It is more likely to be severe and fatal.
Scientists had previously identified that survivors with pathogenic variants in one of 60 different cancer-predisposing genes or any of 127 DNA damage repair genes were more likely to experience a second or subsequent cancer. There was a possibility. This study extends research that shows a direct link between cancer-predisposing variants and increased second-cancer-related mortality.
Many of these genetic variants are known to be associated with cancer. For example, the tumor suppressor gene TP53 is one of 60 genes included in the analysis.
Key to the utility of the discovery is that these variants are present in patients’ DNA when cancer is diagnosed in children, allowing an individualized medical approach to be developed early in life for each survivor.
By better understanding the impact such genes have on future cancer risk and outcome beyond primary childhood cancers, the study will help inform efforts to prevent second cancers and improve outcomes in these individuals.
Senior corresponding author Zhaoming said, “Our study shows that clinical genetic testing can detect whether survivors are carriers of these pathogenic variants, thereby identifying people at higher risk of developing deadly second cancers. Screening and early intervention could potentially save their lives.” Wang, PhD, St. Jude Department of Epidemiology and Cancer Control.
The total number of childhood cancer survivors who develop a second or subsequent cancer is low, and the percentage of survivors who develop a cancer-precursor type is low (~6 percent).
Together, these factors have made it extremely challenging to study and understand the genetic risks for second cancers and their outcomes in this population. To reach statistically meaningful results, Wang and colleagues combined whole genome/exome sequencing and clinical data from more than twelve thousand childhood cancer survivors.
The study combined data from North America’s two largest survival studies, the CCSS and St. Jude Life cohorts.
“This is the first comprehensive study to look at the genetic cause of late mortality – specifically late mortality due to second cancer,” Wang said. “We now know that cancer-predisposing variants contribute to the risk of death from a second cancer.” Increased surveillance may help limit the impact of these cancer-predisposing variants as childhood cancer survivors grow into adulthood. By knowing which survivors are at greater risk, healthcare providers may be able to recommend individualized cancer screening, thereby detecting additional cancers at their earliest and most treatable stage.
These types are the hereditary, or germline, part of the DNA that people are born with. This means they can be detected in children when they are first diagnosed with childhood cancer, giving survivors the knowledge they need to reduce their risk later in life. Is.