Zhaoming Wang, PhD, bioinformatics scientist, Department of Computational Biology, St. Jude Children’s Research Hospital, discusses the utility of genome-wide association studies in pediatric oncology.

The monogenic and polygenic associations to subsequent breast cancer risk in survivors of childhood cancer is currently being studied using whole-genome sequencing data. Although genome-wide associated studies like this have been successful, some in the community have doubts over their clinical utility, Wang says. Although more data are needed to support a clinical recommendation, this is the first instance in which evidence to support common variant effects were found in childhood survivors of cancer.

Wang explains that using a bigger sample size gives a greater picture of what is occurring in these patients. Additionally, Wang says that this is an era in which data like these can be clinically combined with rare mutations that can explain a lot of heritable breast cancers, rather than sporadic. Science is progressing, and there is promise in finding and managing high-risk patients for screening and cancer prevention at early stages.

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Utility of Genome-Wide Association Studies in Pediatric Oncology

Zhaoming Wang, PhD, bioinformatics scientist, Department of Computational Biology, St. Jude Children’s Research Hospital, discusses a study that is identifying the risk of breast cancer in survivors of childhood cancer.

Chest irritation in female pediatric patients with cancer is a major risk factor for breast cancer as survivors move into adulthood, explains Wang. Literature has also reported a risk of breast cancer for these patients after treatment with chemotherapy, but the genetic risk is not known.

In addition to whole-genome sequencing of rare, highly penetrant mutations in the predisposition genes, Wang says that investigators also looked at the genetic variants in these patients. This was done in an attempt to model risk of the commonly used demographic clinical variables and genetic factors, including rare mutations and common variants. From there, a polygenic risk score with 172 variants was built. Wang explains that each patient will receive a number to measure their risk of developing breast cancer in the general population.

The data used in this analysis was taken from the St. Jude Lifetime Cohort Study whole-genome sequencing data. Wang says it is the first time that this type of score was applied to survivors of childhood cancer.

Zhaoming Wang, PhD, bioinformatics scientist, Department of Computational Biology, St. Jude Children’s Research Hospital, discusses a study that is identifying the risk of breast cancer in survivors of childhood cancer.
 

Identifying the Risk of Breast Cancer in Childhood Cancer Survivors

Zhaoming Wang, PhD, bioinformatics scientist, Department of Computational Biology, St. Jude Children’s Research Hospital, discusses the next steps of the St. Jude Lifetime Cohort Study.

Investigators are using the St. Jude Lifetime Cohort Study whole-genome sequencing data in an effort to evaluate the monogenic and polygenic associations to subsequent breast cancer risk in survivors of childhood cancer. The goal of this work is to identify the role of genetic variants and treatment exposures to subsequent risk of breast cancer in adult survivors of childhood cancer.

The central life cohort is expanding, adding at least 1000 more survivors to help refine and validate the study, Wang says. Additionally, there is a multicenter cohort called Childhood Cancer Survivor Study, in which at least 30 different centers have participated nationwide. The whole-exome sequencing of the 5700 patients is complete, so the next step is to bring these data together. That is one of the future directions that investigators are going to pursue.

Next Steps With the St. Jude Lifetime Cohort Study

Zhaoming Wang, PhD, bioinformatics scientist, Department of Computational Biology, St. Jude Children’s Research Hospital, discusses a genomic analysis of breast cancer risk in pediatric cancer survivors.

Researchers did a genomic sequencing assessment on 3000 pediatric cancer survivors, analyzing the pathogenesis of the patients’ germline mutations. The goal was to determine the genomic contribution to the risk of subsequent breast cancer. Preclinical data suggested that the exposure of radiation to the breast tissue during the treatment of pediatric cancer is a major risk factor. Wang adds that literature had also been published indicating that certain chemotherapy agents contributed to increased risk. Genetic risk is currently unknown, Wang says.

Typical clinical demographics were used in the analysis, Wang says, and genomic expressions were factored in. He presented the findings at the 2018 AACR Annual Meeting.

Zhaoming Wang, PhD

Articles

Utility of Genome-Wide Association Studies in Pediatric Oncology

Identifying the Risk of Breast Cancer in Childhood Cancer Survivors

Next Steps With the St. Jude Lifetime Cohort Study

Dr. Wang on Genomic Analysis of Breast Cancer Risk in Pediatric Cancer Survivors