Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls

Mandalenakis, Zacharias; Karazisi, Christina; Skoglund, Kristofer; Rosengren, Annika; Lappas, Georgios; Eriksson, Peter; Dellborg, Mikael

doi:10.1001/jamanetworkopen.2019.6762

Cited by 66 publications

(57 citation statements)

References 26 publications

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“…A recently published study from the Swedish Patient Register showed an overall hazard ratio for cancer of 2.24 in patients with congenital heart disease compared with healthy controls. An even higher hazard ratio of 3.37 is reported in patients born from 1990 to 1993, which fits well to our study group [34]. This study claims that radiation dose from cardiac catherization might not be the only contributor to increased risk of cancer in patients with congenital heart disease.…”

Section: Discussionsupporting

confidence: 90%

Increased Cancer Incidence Following up to 15 Years after Cardiac Catheterization in Infants under One Year between 1980 and 1998—A Single Center Observational Study

Stern

Seidenbusch

Hapfelmeier³

et al. 2020

JCM

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Objective: To evaluate the incidence of cancer within the first 15 years of life in children who underwent cardiac catheterization under the age of one year. Methods: In this retrospective, single center study, 2770 infants (7.8% with trisomy 21) were studied. All infants underwent cardiac catheterization under one year of age between January 1980 and December 1998. Newly diagnosed cancer in the first 15 years of life was assessed through record linkage to the German Childhood Cancer Registry (GCCR). Cancer risk in study patients was compared to the GCCR population of children less than 15 years. Patients with trisomy 21 were compared to the Danish Cytogenic Register for trisomy 21. Effective radiation doses were calculated for each tumor patient and 60 randomly selected patients who did not develop cancer. Results: In total, 24,472.5 person-years were analyzed. Sixteen children developed cancer, while 3.64 were expected (standardized incidence ratio (SIR) = 4.4, 95% confidence interval (CI): 2.5–7.2, p < 0.001). There was no preferred cancer type. The observed incidence of leukemia and solid tumors in trisomy 21 was only slightly higher (1 in 476 py) than expected (1 in 609 py, p = 0.64). There was no direct relationship between the radiation dose and the incidence of cancer. Conclusion: Cardiac catherization in the first year of life was associated with a significantly increased cancer risk in a population with congenital heart disease.

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Section: Discussionsupporting

confidence: 90%

Increased Cancer Incidence Following up to 15 Years after Cardiac Catheterization in Infants under One Year between 1980 and 1998—A Single Center Observational Study

Stern

Seidenbusch

Hapfelmeier³

et al. 2020

JCM

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“…In addition to testicular cancer, our study provided evidence for other associations between birth defects and cancer diagnosed in adulthood. For example, the odds ratio for congenital heart defects and overall cancer was 1.28 (1.02 to 1.59), similar to or lower than those previously suggested for adults 143536. Another example was nervous system defects, with a 15-fold increased risk of cancer before the age of 5, whereas the odds ratio for adults was reduced to 1.76 (1.16 to 2.65).…”

Section: Discussionsupporting

confidence: 73%

“…Previous studies have reported declining risk of cancer with age, but most were limited by size, shorter follow-up time, or both, and few were able to assess specific birth defects 89101112133536. Only three studies included adults, and these evaluated only nervous and circulatory system defects and congenital heart defects 143536. In our study, we found that although the increase in overall cancer risk declined with age, it persisted into adulthood for both non-chromosomal and chromosomal anomalies.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults

Daltveit

Klungsøyr

Engeland

et al. 2020

BMJ

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ObjectiveTo examine associations between birth defects and cancer from birth into adulthood.DesignPopulation based nested case-control study.SettingNationwide health registries in Denmark, Finland, Norway, and Sweden.Participants62 295 cancer cases (0-46 years) and 724 542 frequency matched controls (matched on country and birth year), born between 1967 and 2014.Main outcome measuresRelative risk of cancer in relation to major birth defects, estimated as odds ratios with 99% confidence intervals from logistic regression models.ResultsAltogether, 3.5% (2160/62 295) of cases and 2.2% (15 826/724 542) of controls were born with major birth defects. The odds ratio of cancer for people with major birth defects compared with those without was 1.74 (99% confidence interval 1.63 to 1.84). For individuals with non-chromosomal birth defects, the odds ratio of cancer was 1.54 (1.44 to 1.64); for those with chromosomal anomalies, the odds ratio was 5.53 (4.67 to 6.54). Many structural birth defects were associated with later cancer in the same organ system or anatomical location, such as defects of the eye, nervous system, and urinary organs. The odds ratio of cancer increased with number of defects and decreased with age, for both non-chromosomal and chromosomal anomalies. The odds ratio of cancer in people with any non-chromosomal birth defect was lower in adults (≥20 years: 1.21, 1.09 to 1.33) than in adolescents (15-19 years: 1.58, 1.31 to 1.90) and children (0-14 years: 2.03, 1.85 to 2.23). The relative overall cancer risk among adults with chromosomal anomalies was markedly reduced from 11.3 (9.35 to 13.8) in children to 1.50 (1.01 to 2.24). Among adults, skeletal dysplasia (odds ratio 3.54, 1.54 to 8.15), nervous system defects (1.76, 1.16 to 2.65), chromosomal anomalies (1.50, 1.01 to 2.24), genital organs defects (1.43, 1.14 to 1.78), and congenital heart defects (1.28, 1.02 to 1.59) were associated with overall cancer risk.ConclusionsThe increased risk of cancer in individuals with birth defects persisted into adulthood, both for non-chromosomal and chromosomal anomalies. Further studies on the molecular mechanisms involved are warranted.

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“…There have been several epidemiologic studies associated with childhood congenital malformations with cancer risk. In a recent study from the Swedish Patient Register, e.g., Mandalenakis et al 26 showed that C-AYA patients with any kind of CHD had increased risk of developing cancer (hazard ratio = 2.24, 95% CI, 2.01-2.48) compared to their matched controls, from Total Population Register in Sweden, who did not have CHD (2% vs. 0.9%). Here, we also showed that 67 (4.4%) of our C-AYA patients with solid tumors carried at least one germline P/LP variant in a CHD-related gene (7 KCPG and 19 candidate genes) ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

et al. 2020

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Compared to adult carcinomas, there is a paucity of targeted treatments for solid tumors in children, adolescents, and young adults (C-AYA). The impact of germline genomic signatures has implications for heritability, but its impact on targeted therapies has not been fully appreciated. Performing variant-prioritization analysis on germline DNA of 1,507 C-AYA patients with solid tumors, we show 12% of these patients carrying germline pathogenic and/ or likely pathogenic variants (P/LP) in known cancer-predisposing genes (KCPG). An additional 61% have germline pathogenic variants in non-KCPG genes, including PRKN, SMAR-CAL1, SMAD7, which we refer to as candidate genes. Despite germline variants in a broad gene spectrum, pathway analysis leads to top networks centering around p53. Our drugtarget analysis shows 1/3 of patients with germline P/LP variants have at least one druggable alteration, while more than half of them are from our candidate gene group, which would otherwise go unidentified in routine clinical care.

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Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls

Cited by 66 publications

References 26 publications

Increased Cancer Incidence Following up to 15 Years after Cardiac Catheterization in Infants under One Year between 1980 and 1998—A Single Center Observational Study

Increased Cancer Incidence Following up to 15 Years after Cardiac Catheterization in Infants under One Year between 1980 and 1998—A Single Center Observational Study

Cancer risk in individuals with major birth defects: large Nordic population based case-control study among children, adolescents, and adults

Comprehensive germline genomic profiles of children, adolescents and young adults with solid tumors

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