Establishment of a Lifetime Cohort of Individuals Surviving Childhood Cancer
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PROVIDER: PRJNA1023683 | ENA |
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Project description:BackgroundSurvivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer.MethodsThe St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis.FindingsOf 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs.InterpretationThe burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population.FundingThe US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.
| S-EPMC5798235 | biostudies-literature
Project description:BackgroundTo facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children's Research Hospital (SJCRH) is establishing a lifetime cohort of survivors.MethodsEligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: (1) diagnosis of childhood malignancy treated at SJCRH; (2) survival ≥ 10 years from diagnosis; and (3) current age ≥ 18 years. Three levels of participation are offered: (1) comprehensive evaluation on SJCRH campus; (2) limited home evaluation; or (3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies.ResultsAs of January 1, 2010, 1,625 (42%) of 3,900 eligible ≥ 10-year survivors have been contacted. Among the first 1,000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (P = 0.001).ConclusionsEarly results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments.
| S-EPMC3088729 | biostudies-literature
Project description:Childhood abuse significantly increases the lifetime risk of negative mental health outcomes, including psychiatric disorders, such as depression and suicide. While clinical and epidemiological associations are well characterized, the molecular mechanisms through which adverse experiences in early life influence mental health outcomes over the lifespan remain unclear. In this study, we employed laser capture microdissection followed by RNA sequencing (LCM-seq) to investigate transcriptomic alterations to prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse (N=24) in comparison to controls (N = 21). We first showed that LCM-seqproduced high-quality transcriptomic data that was strongly enriched for our cell type of interest (95.8% contribution). Differential expression analysis revealed119 genes that were altered between cases versus controls. Using weighted correlation network analysis (WGCNA) we next identified a network of downregulated genes, in individuals with a history of childhood abuse (r = -0.30, p = 0.04), that was enriched in pathways related to nervous system development and plasticity. The eigengene of this network was significantly correlated (r(23) = 0.490, p = 0.021) with average cell body volume of deep-layer pyramidal neurons. Of the 1042 mRNA genes within this network, 81 were differentially expressed between cases and controls. Using high-throughput qPCR, and comparing with an additional group of depressed subjects who died by suicide without a history of childhood abuse (N = 29), we found 7 genes whose expression levels were significantly (p < 0.05) predicted by a history of childhood abuse but not major depressive disorder and suicide.Our study, therefore, advances our understanding of the long term impact of childhood abuse and points to some of the molecular pathways that may underly previously observed alterations innervous system development and plasticity.
2022-12-30 | GSE157197 | GEO
Project description:Long-term survivors of childhood cancer experience treatment-related cardiotoxicity among a broad spectrum of chronic health conditions, which may be further aggrevated by suboptimal life-course social/behavioral/environmental exposures. Epigenetic mechanisms, particularly DNA methylation (DNAm), provide a potential link through which these exposures become biologically embedded and subsequently influence long-term health outcomes. Epigenome-wide association studies (EWAS) identified DNAm signatures associated with both treatment effects as well as life-course exposures. In parallel, DNAm variations were also evaluated in relation to cardiometabolic risk factors, cardiovascular diseases, and other chronic health conditions, revealing individual CpG sites or genes/geomic regions where these CpGs reside linked to clinically relevant phenotypes. Together, these findings support DNAm as a molecular interface connecting diverse exposures to adverse health outcomes. In addition, epigenetic age acceleration, assessed using DNAm-based aging biomarkers, was observed among survivors exposed to cancer treatments. Epigenetic age acceleration mediated a substantial proportion of the associations between cancer treatment exposures and cardiometabolic risk factors or cardiovascular diseases, supporting accelerated biological aging as a key pathway linking cancer treatment to long-term morbidity. Lifestyle and health behaviors, as well as social vulnerability and psychosocial stress, were also associated with variations in epigenetic age acceleration, highlighting the potential modifiability of aging-related pathways in ameliorating late-effects among childhood cancer survivors. In conclusion, these findings establish DNAm—captured through EWAS signatures and epigenetic age acceleration—as central molecular mechanisms linking treatment effects and life-course exposures to cardiotoxicity along with other chronic health conditions in childhood cancer survivors. This integrative epigenetic framework supports the use of DNAm-based biomarkers for risk stratification and nominates modifiable pathways as potential intervention targets to improve long-term survivorship outcomes.
2026-01-13 | GSE314261 | GEO
Project description:In this dataset, we include the expression data obtained from KRas expressing tumors, matched Kras expressing tumor spheres, surviving cells and surviving cells after KRas re-expression for 24hs
2014-06-09 | GSE58307 | GEO
Project description:In this dataset, we include the expression data obtained from KRas expressing tumors, matched Kras expressing tumor spheres, surviving cells and surviving cells after KRas re-expression for 24hs Data reported here are obtained from 5 independent tumors (from 1 to 5). For each tumor, expression data for the original Tumor (in vivo bulk tumor lesion), the KRas Expressing Spheres derived from the bulk tumor, the matched surviving cells after 8 days of KRas ablation (SCs) and Surviving Cells after 24 hours of KRas re-expression are reported.
2014-06-09 | E-GEOD-58307 | biostudies-arrayexpress
Project description:Epigenome-wide DNA Methylation Profiling in the Investigation of Treatment and Life-Course Exposures and Adverse Health Outcomes in Survivors of Childhood Cancer from the St. Jude Lifetime Cohort
| PRJNA1390672 | ENA
Project description:Greater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways.
2024-12-31 | GSE232352 | GEO