Skip directly to search Skip directly to A to Z list Skip directly to navigation Skip directly to page options Skip directly to site content

Search PHGKB:

Last Posted: Jan 09, 2023
spot light Highlights

Heterozygous BRCA1/2 and Mismatch Repair Gene Pathogenic Variants in Children and Adolescents with Cancer.
Kratz Christian P et al. Journal of the National Cancer Institute 2022 8

We conducted a meta-analysis of 11 studies that incorporated comprehensive germline testing for children and adolescents with cancer. ClinVar pathogenic/likely pathogenic variants (PVs) in genes of interest were compared to two control groups. Results were validated in a cohort of mainly European cases and controls. Among 3,975 children/adolescents with cancer, significant associations with cancer risk were observed for PVs in BRCA1/2 (26 PVs vs 63 PVs among 27,501 controls, OR 2.78, 95%-CI 1.69—4.45, p<.001) and mismatch repair (MMR) genes (19 PVs vs 14 PVs among 27,501 controls, OR 7.33, 95%-CI 3.64—14.82, p<.001).

Predicting chronic morbidity in childhood cancer survivors.
Vrooman Lynda M et al. Nature medicine 2022 8

Approximately 85% of children diagnosed with cancer will be cured of their primary cancer, but epidemiologic and clinical studies have characterized a significant burden of morbidity, as well as excess early mortality, in survivors. Two recent studies show that incorporating genetic factors into risk models improves the prediction of severe obesity for survivors of childhood cancer, which could promote early interventions and better long-term care.

Genetic risk score enhances the risk prediction of severe obesity in adult survivors of childhood cancer.
Sapkota Yadav et al. Nature medicine 2022 7

We show the contribution of genetic risk scores (GRSs) to increase prediction of those survivors of childhood cancer who are at risk for severe obesity (body mass index =40?kg?m-2) as an adult. Among 2,548 individuals of European ancestry from the St. Jude Lifetime Cohort Study who were 5-year survivors of childhood cancer, the GRS was found to be associated with 53-fold-higher odds of severe obesity. Addition of GRSs to risk prediction models based on cancer treatment exposures and lifestyle factors significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in the identification of 4.3-times more high-risk survivors).

Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer
Q Dong et al, Genome Medicine, March 22, 2022

Increased epigenetic age acceleration (EAA) in survivors of childhood cancer is associated with specific treatment exposures, unfavorable health behaviors, and presence of certain chronic health conditions. To better understand inter-individual variability, we investigated the genetic basis underlying EAA. We identified novel genetic variants in the SELP gene and HLA region associated with EAA-Horvath and EAA-Hannum, respectively, among survivors of childhood cancer.

Disclaimer: Articles listed in the Public Health Genomics and Precision Health Knowledge Base are selected by the CDC Office of Public Health Genomics to provide current awareness of the literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the update, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.