Childhood Cancer Predisposition: An Overview for the General Pediatrician

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Laura Kagami ◽  
Sarah Baldino ◽  
Suzanne P. MacFarland
Keyword(s):  
Childhood Cancer ◽  
Cancer Predisposition ◽  
General Pediatrician

scholarly journals Selection criteria for assembling a pediatric cancer predisposition syndrome gene panel

2021 ◽  
Author(s):  
Anna Byrjalsen ◽  
Illja J. Diets ◽  
Jette Bakhuizen ◽  
Thomas van Overeem Hansen ◽  
Kjeld Schmiegelow ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Pediatric Cancer ◽  
Causal Relation ◽  
Evaluation Criteria ◽  
Cancer Predisposition ◽  
Gene Panel ◽  
Childhood Onset ◽  
Children With Cancer ◽  
Cancer Predisposition Syndrome ◽  
A Prospective Study

AbstractIncreasing use of genomic sequencing enables standardized screening of all childhood cancer predisposition syndromes (CPS) in children with cancer. Gene panels currently used often include adult-onset CPS genes and genes without substantial evidence linking them to cancer predisposition. We have developed criteria to select genes relevant for childhood-onset CPS and assembled a gene panel for use in children with cancer. We applied our criteria to 381 candidate genes, which were selected through two in-house panels (n = 338), a literature search (n = 39), and by assessing two Genomics England’s PanelApp panels (n = 4). We developed evaluation criteria that determined a gene’s eligibility for inclusion on a childhood-onset CPS gene panel. These criteria assessed (1) relevance in childhood cancer by a minimum of five childhood cancer patients reported carrying a pathogenic variant in the gene and (2) evidence supporting a causal relation between variants in this gene and cancer development. 138 genes fulfilled the criteria. In this study we have developed criteria to compile a childhood cancer predisposition gene panel which might ultimately be used in a clinical setting, regardless of the specific type of childhood cancer. This panel will be evaluated in a prospective study. The panel is available on (pediatric-cancer-predisposition-genepanel.nl) and will be regularly updated.

scholarly journals Cancer predisposition syndromes as risk factor for early second primary neoplasms after childhood cancer - a national cohort study

2020 ◽  
Author(s):  
Nicolas Waespe ◽  
Fabien Naomi Belle ◽  
Shelagh Redmond ◽  
Christina Schindera ◽  
Ben Daniel Spycher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Childhood Cancer ◽  
Cancer Patients ◽  
Cumulative Incidence ◽  
Cancer Predisposition ◽  
Second Primary ◽  
Hematopoietic Stem ◽  
Second Primary Neoplasms ◽  
Primary Neoplasms

Background: Childhood cancer patients are at increased risk of second primary neoplasms (SPNs). We assessed incidence and risk factors for early SPNs with a focus on cancer predisposition syndromes (CPSs). Patients and methods: This cohort study used data from the Swiss Childhood Cancer Registry. We included patients with first primary neoplasms (FPN) until age 21 years from 1986 to 2015 and identified SPNs occurring before age 21. We calculated standardized incidence ratios (SIR) and absolute excess risks (AER) using Swiss population cancer incidence data and cumulative incidence of SPNs. We calculated hazard ratios (HR) of risk factors for SPNs using Fine and Gray competing risk regression. Results: Among 8,074 childhood cancer patients, 304 (4%) were diagnosed with a CPS and 94 (1%) developed early SPNs. The incidence of SPNs was more than 10-fold increased in childhood cancer patients compared to neoplasms in the general population (SIR 10.6, 95%-confidence interval [CI] 8.7-13.1) and the AER was 179/100,000 person-years (CI 139-219). Cumulative incidence of SPNs 20 years after FPN diagnosis was 23% in patients with CPSs and 3% in those without. Risk factors for SPNs were CPSs (HR 7.8, CI 4.8-12.7), chemotherapy (HR 2.2, CI 1.1-4.6), radiotherapy (HR 1.9, CI 1.2-2.9), hematopoietic stem cell transplantation (HR 1.8, CI 1-3.3), and older age (15-20 years) at FPN diagnosis (HR 1.9, CI 1.1-3.2). Conclusion: CPSs are associated with a high risk of SPNs before age 21 years. Identification of CPSs is important for appropriate cancer surveillance and targeted screening.

Successful integration of genetic counseling in a comprehensive childhood cancer survivorship clinic.

2017 ◽  
Vol 35 (5_suppl) ◽  
pp. 230-230
Author(s):  
Shafqat Shah ◽  
Gregory John Aune ◽  
Lindsey Mette ◽  
Natalie Poullard
Keyword(s):  
Genetic Counseling ◽  
Genetic Testing ◽  
Family History ◽  
Childhood Cancer ◽  
Cancer Survivorship ◽  
Chart Review ◽  
Genetic Counselor ◽  
Pilot Project ◽  
Cancer Predisposition ◽  
Childhood Cancer Survivorship

230 Background: Awareness of inherited genetic risk and cancer predisposition has markedly increased. Research has shown that germline mutations in known cancer predisposition genes are identified in ~8% of pediatric oncology patients. Patients diagnosed years ago did not meet with a Genetic counselor or undergo genetic testing. The annual comprehensive survivorship visit provides cancer survivors an opportunity to review personal and family history and receive Genetic counseling. Methods: Our group initiated a pilot project in our Childhood Cancer Survivorship clinic (CCSC) to assess the feasibility of introducing survivors to a Certified Genetic Counselor (CGC). Initially, a chart review of annual visits that took place over a 3-month period was performed. A record of documentation of family history and genetic counseling was made. During the pilot period, survivors and their families were given the option to meet with a CGC. The CGC prepared a pedigree and made specific written recommendations regarding the indication, if any, for genetic testing in the patient or family. Anonymous post-counseling surveys were mailed to the families to gauge their satisfaction. Results: Prior to the pilot, 38 survivors were seen for annual visits over a 3 month period. Chart review identified no formal genetic counseling. A note of a family history of cancer was made in 1 patient. During the 3 month implementation period, 50 survivors were seen for annual visits. Thirty-four ( ~70%) accepted the offer to see a CGC. Of the 16 that did not meet with a CGC, 3 had significant medical issues that required attention, 2 had Down syndrome and 2 had previous genetic counseling. The rest declined interest with no specific rationale. Very few (3) surveys were returned. All rated the experience highly. Conclusions: Our experience in a multi-disciplinary CCSC supports the feasibility of delivering CGC services to long-term survivors of cancer. A majority of survivors were interested in meeting with the CGC. Further development of this program will focus on educating survivors about cancer predisposition and increasing access to CGC services.

Utility of a Cancer Predisposition Screening Tool for Predicting Subsequent Malignant Neoplasms in Childhood Cancer Survivors

2021 ◽  
pp. JCO.21.00018
Author(s):  
Noelle Cullinan ◽  
Ian Schiller ◽  
Giancarlo Di Giuseppe ◽  
Mohammed Mamun ◽  
Lara Reichman ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Conditional Logistic Regression ◽  
Childhood Cancer Survivors ◽  
Cancer Predisposition ◽  
Malignant Neoplasms ◽  
Primary Cancer ◽  
Primary Malignancy ◽  
Control Approach ◽  
Cancer Predisposition Syndrome

PURPOSE Childhood cancer survivors (CCS) are at risk of developing subsequent malignant neoplasms (SMNs) resulting from exposure to prior therapies. CCS with underlying cancer predisposition syndromes are at additional genetic risk of SMN development. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) tool identifies children with cancer at increased likelihood of having a cancer predisposition syndrome, guiding clinicians through a series of Yes or No questions that generate a recommendation for or against genetic evaluation. We evaluated MIPOGG's ability to predict SMN development in CCS. METHODS Using the provincial cancer registry (Ontario, Canada), and adopting a nested case-control approach, we identified CCS diagnosed and/or treated for a primary malignancy before age 18 years (1986-2015). CCS who developed an SMN (cases) were matched, by primary cancer and year of diagnosis, with CCS who did not develop an SMN (controls) over the same period (1:5 ratio). Potential predictors for SMN development (chemotherapy, radiation, and MIPOGG output) were applied retrospectively using clinical data pertaining to the first malignancy. Conditional logistic regression models estimated hazard ratios and 95% CIs associated with each covariate, alone and in combination, for SMN development. RESULTS Of 13,367 children with a primary cancer, 317 (2.4%) developed an SMN and were matched to 1,569 controls. A MIPOGG output recommending evaluation was significantly associated with SMN development (hazard ratio 1.53; 95% CI, 1.06 to 2.19) in a multivariable model that included primary cancer therapy exposures. MIPOGG was predictive of SMN development, showing value in nonhematologic malignancies and in CCS not exposed to radiation. CONCLUSION MIPOGG has additional value for SMN prediction beyond treatment exposures and may be beneficial in decision making for enhanced individualized SMN surveillance strategies for CCS.

scholarly journals Cancer predisposition syndromes as a risk factor for early second primary neoplasms after childhood cancer – A national cohort study

2021 ◽  
Vol 145 ◽  
pp. 71-80
Author(s):  
Nicolas Waespe ◽  
Fabiën N. Belle ◽  
Shelagh Redmond ◽  
Christina Schindera ◽  
Ben D. Spycher ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cohort Study ◽  
Childhood Cancer ◽  
Cancer Predisposition ◽  
Second Primary ◽  
Second Primary Neoplasms ◽  
National Cohort ◽  
Primary Neoplasms

scholarly journals Predictors for participation in DNA self-sampling of childhood cancer survivors in Switzerland

2021 ◽  
Author(s):  
Nicolas Waespe ◽  
Sven Strebel ◽  
Denis Marino ◽  
Veneranda Mattiello ◽  
Fanny Muet ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Age Groups ◽  
Childhood Cancer Survivors ◽  
Cross Sectional Study ◽  
Cancer Predisposition ◽  
Second Primary ◽  
Cross Sectional ◽  
Cancer Predisposition Syndrome ◽  
Foreign Nationality

Research on germline genetic variants relies on a sufficient number of eligible participants which is difficult to achieve for rare diseases such as childhood cancer. With self-collection kits using saliva or buccal swabs, participants can contribute genetic samples conveniently from their home. We identified determinants of participation in DNA self-collection in this cross-sectional study. We invited 928 childhood cancer survivors in Switzerland with a median age of 26.5 years (interquartile range 18.8-36.5), of which 463 (50%) participated. Foreign nationality (odds ratio [OR] 0.5, 95%-confidence interval [CI] 0.4-0.7), survivors aged 30-39 years at study versus other age groups (OR 0.5, CI 0.4-0.8), and those with a known cancer predisposition syndrome (OR 0.5, CI 0.3-1.0) participated less. Survivors with a second primary neoplasm (OR 1.9, CI 1.0-3.8) or those living in a French or Italian speaking region (OR 1.3, 1.0-1.8) tended to participate more. We showed that half of survivors participate in germline DNA self-sampling relying completely on mailing of sample kits. Foreign nationality, age 30-39 years, and cancer predisposition syndromes were associated with less participation. More targeted recruitment strategies may be advocated for these subgroups. To increase participation in DNA self-sampling, understanding and perceptions of survivors need to be better understood.

Genetic Predisposition to Childhood Cancer in the Genomic Era

2019 ◽  
Vol 20 (1) ◽  
pp. 241-263 ◽  
Author(s):  
Sharon E. Plon ◽  
Philip J. Lupo
Keyword(s):  
Childhood Cancer ◽  
Pediatric Cancer ◽  
Association Studies ◽  
Cancer Predisposition ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Pathogenic Variants ◽  
Pediatric Cancer Patients ◽  
Genes Encoding ◽  
Genome Analyses

Developments over the past five years have significantly advanced our ability to use genome-scale analyses—including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing—to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: ( a) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, ( b) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, ( c) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and ( d) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7–10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.

Sign in / Sign up

Export Citation Format

Share Document