1. Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease
- Author
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Alexandre C. Pereira, Deepak Srivastava, Jonathan G. Seidman, Sarah U. Morton, Richard P. Lifton, Peter E. Newburger, Alessandro Giardini, Jane W. Newburger, Daniel Quiat, Wendy K. Chung, Christine E. Seidman, Akiko Shimamura, Elizabeth Goldmuntz, Martina Brueckner, Alexander R. Opotowsky, Daniel Bernstein, Richard W. Kim, Bruce D. Gelb, Sheng Chih Jin, Yufeng Shen, George A. Porter, Martin Tristani-Firouzi, and Michelle Gurvitz
- Subjects
Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Heart disease ,Adolescent ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Gene Frequency ,Loss of Function Mutation ,Internal medicine ,Neoplasms ,Genotype ,medicine ,Online First ,Humans ,Genetic Predisposition to Disease ,030212 general & internal medicine ,cardiovascular diseases ,Child ,Allele frequency ,Gene ,Aged ,Aged, 80 and over ,business.industry ,Research ,Brief Report ,Infant, Newborn ,Cancer ,Genetic Variation ,Infant ,Odds ratio ,Middle Aged ,medicine.disease ,Gene Expression Regulation ,Case-Control Studies ,Child, Preschool ,Cohort ,Female ,Cardiology and Cardiovascular Medicine ,Cancer risk ,business ,Genes, Neoplasm - Abstract
Key Points Question Do damaging gene variants account for increased cancer risk in patients with congenital heart disease (CHD)? Findings In this case-control study, loss-of-function variants in cancer risk genes were increased approximately 1.3-fold in 4443 patients with CHD compared with 9808 control participants. This burden was highest in cancer risk genes previously associated with CHD (7.2-fold) or that regulate gene expression (1.9-fold); patients with CHD and extracardiac anomalies and/or neurodevelopmental delay had the highest rates of damaging variants in cancer risk genes. Meaning Genetic analyses of patients with CHD may identify precise causes of heart malformations and also patients with CHD and increased cancer risks., This case-control study compares the frequency of damaging cancer risk gene variants in patients with congenital heart disease vs control participants and identifies associated clinical variables., Importance Patients with congenital heart disease (CHD), the most common birth defect, have increased risks for cancer. Identification of the variables that contribute to cancer risk is essential for recognizing patients with CHD who warrant longitudinal surveillance and early interventions. Objective To compare the frequency of damaging variants in cancer risk genes among patients with CHD and control participants and identify associated clinical variables in patients with CHD who have cancer risk variants. Design, Setting, and Participants This multicenter case-control study included participants with CHD who had previously been recruited to the Pediatric Cardiac Genomics Consortium based on presence of structural cardiac anomaly without genetic diagnosis at the time of enrollment. Permission to use published sequencing data from unaffected adult participants was obtained from 2 parent studies. Data were collected for this study from December 2010 to April 2019. Exposures Presence of rare (allele frequency
- Published
- 2020