Estimated number of adult survivors of childhood cancer in United States with cancer-predisposing germline variants.

Wilson CL1, Wang Z1,2, Liu Q3, Ehrhardt MJ1,4, Mostafavi R1, Easton J2, Mulder H2, Hedges DJ5, Wang S1,2, Rusch M2, Edmonson M2, Levy S6, Lanctot JQ1, Currie K1, Lear M5, Patel A2, Sapkota Y1, Brooke RJ1, Moon W1, Chang TC2, Chen W2, Kesserwan CA4, Wu G2, Nichols KE4, Hudson MM1,4, Zhang J2, Robison LL1, Yasui Y1.

Author information

1: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
2: Departments of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.
3: School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
4: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
5: Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee.
6: Genomics Service Laboratory, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.

Abstract

PURPOSE:

To estimate the absolute number of adult survivors of childhood cancer in the U.S. population who carry a pathogenic or likely pathogenic variant in a cancer predisposition gene.

METHODS:

Using the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated the number of childhood cancer survivors on December 31, 2016 for each childhood cancer diagnosis, multiplied this by the proportion of carriers of pathogenic/likely pathogenic variants in the St. Jude Lifetime Cohort (SJLIFE) study, and projected the resulting number onto the U.S.

POPULATION:

RESULTS:

Based on genome sequence data, 11.8% of 2450 SJLIFE participants carry a pathogenic/likely pathogenic variant in one of 156 cancer predisposition genes. Given this information, we estimate that 21 800 adult survivors of childhood cancer in the United States carry a pathogenic/likely pathogenic variant in one of these genes. The highest estimated absolute number of variant carriers are among survivors of central nervous system tumors (n = 4300), particularly astrocytoma (n = 1800) and other gliomas (n = 1700), acute lymphoblastic leukemia (n = 4300), and retinoblastoma (n = 3500). The most frequently mutated genes are RB1 (n = 3000), NF1 (n = 2300), and BRCA2 (n = 800).

CONCLUSION:

Given the increasing number of childhood cancer survivors in the United States, clinicians should counsel survivors regarding their potential genetic risk, consider referral for genetic counseling and testing, and, as appropriate, implement syndrome-specific cancer surveillance or risk-reducing measures.