scholarly journals Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

2021 ◽  
Author(s):  
Silvia Ravera ◽  
Tiziana Vigliarolo ◽  
Silvia Bruno ◽  
Fabio Morandi ◽  
Danilo Marimpietri ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Antioxidant Defenses ◽  
Elderly Subjects ◽  
Cancer Type ◽  
Metabolism Regulation ◽  
Increased Risk ◽  
Early Aging ◽  
The Impact

ABSTRACTPurposeSurvival rates of Childhood Cancer Patients have improved tremendously over the past four decades. However, cancer treatments are associated with an increased risk of developing an anticipated onset of chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in Childhood Cancer Survivors (CCS).Patients and MethodsBiochemical, proteomic and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, comparing the results with those obtained on MNCs of 154 healthy subjects.ResultsData demonstrate that CCS-MNCs show: i) inefficient oxidative phosphorylation associated with low energy status and a metabolic switch to lactate fermentation compared with age-matched normal controls; ii) increment of lipid peroxidation due to an unbalance among the oxidative stress production and the activation of the antioxidant defenses; (iii) significantly lower expression of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-α, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. The application of a mathematical model based on biochemical parameters predicts that CCS have a biological age significantly increased by decades compared to the chronological age. Overall, the results show that the impact of chemo/chemoradiotherapy on mitochondria efficiency in 196 CCS was rather homogeneous, irrespective of cancer type, treatment protocols, and time elapsed from the end of the curative period.ConclusionsOur study identifies some biochemical and molecular alterations possibly contributing to the pathophysiology of anticipated aging and metabolic deficiency described in CCS. These results may be useful in identifying approaches to restore the mitochondrial function, slowing down the aging and the associated pathological conditions in CCS.

scholarly journals Identification of Biochemical and Molecular Markers of Early Aging in Childhood Cancer Survivors

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5214
Author(s):  
Silvia Ravera ◽  
Tiziana Vigliarolo ◽  
Silvia Bruno ◽  
Fabio Morandi ◽  
Danilo Marimpietri ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Mononuclear Cells ◽  
Survival Rates ◽  
Childhood Cancer Survivors ◽  
Elderly Subjects ◽  
Energy Status ◽  
Molecular Alterations ◽  
Metabolism Regulation ◽  
Early Aging

Survival rates of childhood cancer patients have improved over the past four decades, although cancer treatments increase the risk of developing chronic diseases typical of aging. Thus, we aimed to identify molecular/metabolic cellular alterations responsible for early aging in childhood cancer survivors (CCS). Biochemical, proteomic, and molecular biology analyses were conducted on mononuclear cells (MNCs) isolated from peripheral blood of 196 CCS, the results being compared with those obtained on MNCs of 154 healthy subjects. CCS-MNCs showed inefficient oxidative phosphorylation associated with low energy status, and increased lipid peroxidation and lactate fermentation compared with age-matched normal controls. According to a mathematical model based on biochemical parameters, CCS-MNCs showed significantly higher metabolic ages than their real ages. The dysfunctional metabolism of CCS-MNCs is associated with lower expression levels of genes and proteins involved in mitochondrial biogenesis and metabolism regulation, such as CLUH, PGC1-alpha, and SIRT6 in CCS, not observed in the age-matched healthy or elderly subjects. In conclusion, our study identified some biochemical and molecular alterations possibly contributing to the pathophysiology of aging and metabolic deficiencies in CCS. These results identify new targets for pharmacological interventions to restore mitochondrial function, slowing down the aging-associated pathologies in CCS.

scholarly journals Validation of questionnaire-reported chest wall abnormalities with a telephone interview in Swiss childhood cancer survivors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rahel Kasteler ◽  
Christa Lichtensteiger ◽  
Christina Schindera ◽  
Marc Ansari ◽  
Claudia E. Kuehni ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Chest Wall ◽  
Daily Life ◽  
Well Being ◽  
Childhood Cancer Survivors ◽  
Thoracic Wall ◽  
Medical Attention ◽  
The Impact

Abstract Background Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors. Methods We investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors. Results Forty-eight of 2382 (95%CI 2–3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16–20 years; OR 2.5, 95%CI 1.0–6.1), lymphoma (OR 3.8, 95%CI 1.2–11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0–30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0–4.2), surgery to the chest (OR 4.5, 95%CI 1.8–11.5), or chemotherapy (OR 2.9, 95%CI 1.0–8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors. Conclusion It is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Hypothalamic-Pituitary and Other Endocrine Surveillance Among Childhood Cancer Survivors

2021 ◽  
Author(s):  
Laura van Iersel ◽  
Renee L Mulder ◽  
Christian Denzer ◽  
Laurie E Cohen ◽  
Helen A Spoudeas ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Healthcare Providers ◽  
Clinical History ◽  
Childhood Cancer Survivors ◽  
Adolescent And Young Adult ◽  
Endocrine Disorders ◽  
Psychosocial Effects ◽  
Increased Risk ◽  
International Experts

Abstract Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research.

The impact of CNS-directed treatment on quality of life in childhood cancer survivors

2021 ◽  
Author(s):  
Keagan G. Lipak ◽  
Joseph R. Rausch ◽  
Rachel S. Fisher ◽  
Kemar V. Prussien ◽  
Olivia E. Clark ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
The Impact

scholarly journals Cycling Through Cancer: Exploring Childhood Cancer Survivors’ Experiences of Well- and Ill-Being

2017 ◽  
Vol 34 (4) ◽  
pp. 345-361 ◽  
Author(s):  
Shaunna M. Burke ◽  
Jennifer Brunet ◽  
Amanda Wurz ◽  
Christina Butler ◽  
Andrea Utley
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Case Analysis ◽  
Childhood Cancer Survivors ◽  
Study Approach ◽  
Multiple Case ◽  
Multiple Domains ◽  
Physical Changes ◽  
Cross Case Analysis ◽  
The Impact

The benefits of informal physical activity during recovery from childhood cancer have rarely been investigated. This study adopted a multiple case study approach to explore the impact of recreational cycling on childhood cancer survivors’ experiences of well- and ill-being. Three semistructured interviews were conducted over a 3-month period with four survivors to explore their experiences of physical, psychological, and social well- and ill-being. Within-case analysis followed by cross-case analysis identified three themes that captured their well- and ill-being experiences with recreational cycling and cancer: (a) cultivating feelings and emotions, (b) experiencing physical changes, and (c) encountering positive and negative social interactions. The results from this study show that recreational cycling may be a useful adjunct to conventional treatments for the self-management of multiple domains of well- and ill-being during recovery from childhood cancer.

Genetic and treatment risks for diabetes mellitus (DM) in survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) and St. Jude Lifetime (SJLIFE) cohorts.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10014-10014
Author(s):  
Melissa A. Richard ◽  
Sogol Mostoufi-Moab ◽  
Nisha Rathore ◽  
Austin L. Brown ◽  
Stephen J. Chanock ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Childhood Cancer ◽  
Regulatory Region ◽  
Childhood Cancer Survivors ◽  
Population Based ◽  
European Ancestry ◽  
Radiation Group ◽  
Increased Risk

10014 Background: Childhood cancer survivors face increased risk for DM, a polygenic trait also attributable to cancer treatment exposures, particularly abdominal radiation. We aimed to characterize the role of genetic and treatment risk factors for DM among two large cohorts of childhood cancer survivors. Methods: We performed a nested case-control genome-wide association study for DM managed with oral medications in the original CCSS cohort (diagnosed 1970-1986). Logistic regression was conducted in the total sample (N = 5083) and stratified by 1) European ancestry (EA) and 2) abdominal radiation. Replication of suggestive variants (P < 1×10-7) using Fisher’s exact test was performed in independent cohorts: i) CCSS expansion diagnosed 1987-1999 (N = 2588) and ii) SJLIFE diagnosed 1962-2012 (N = 2182). To evaluate the effect of cancer treatment on the background genetic predisposition to DM, we estimated standardized effect sizes (Z’) among EA survivors in each abdominal radiation group for 398 index variants from the largest population-based EA DM study. Radiation group Z’ estimates were compared using linear regression. Results: In the original CCSS cohort we identified nine variants associated with DM and provide further support for four linked variants in the ERCC6L2 locus. Among all survivors, the rs55849673-A allele was associated with increased odds for DM among survivors in the original CCSS cohort (minor allele frequency [MAF]-cases = 0.055; MAF-controls = 0.024; adjusted odds ratio [aOR] = 2.9, 95% CI: 2.0-4.2, P = 3.7×10-8). Allele frequencies were consistent in the CCSS expansion (MAF-cases = 0.075; MAF-controls = 0.028; P = 0.07) and SJLIFE (MAF-cases = 0.036; MAF-controls = 0.027; P = 0.5). Additionally, rs55849673-A estimates were consistent among EA survivors and stronger among survivors not treated with abdominal radiation (MAF-cases = 0.052; MAF-controls = 0.021; aOR = 3.6, P = 1.6×10-6). Notably, in the CCSS expansion all rs55849673-A EA carriers who developed DM did not receive abdominal radiation (MAF-cases = 0.1; MAF-controls = 0.026; P = 0.04). More broadly, the Z’ of population-based DM index variants were 78% lower in survivors treated with abdominal radiation than survivors not treated with abdominal radiation (beta = 0.22; P = 0.01), indicating the background genetic risk for DM may be altered by treatment. Conclusions: We provide evidence for a novel locus of DM in childhood cancer survivors. This locus is a regulatory region associated with expression of ERCC6L2, a gene implicated in an East Asian population-based DM study. Taken together, our findings support the overwhelming effect of abdominal radiation on DM risk in childhood cancer survivors, relative to other risk factors, and provide insight on a genetic locus that may be useful for DM risk prediction in the context of cancer treatment.

scholarly journals Increased Risk of All Cardiovascular Disease Subtypes Among Childhood Cancer Survivors

Circulation ◽  
2019 ◽  
Vol 140 (12) ◽  
pp. 1041-1043 ◽  
Author(s):  
Ashna Khanna ◽  
Priscila Pequeno ◽  
Sumit Gupta ◽  
Paaladinesh Thavendiranathan ◽  
Douglas S. Lee ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Childhood Cancer Survivors ◽  
Increased Risk ◽  
Disease Subtypes

scholarly journals Subsequent Neoplasms After a Primary Tumor in Individuals With Neurofibromatosis Type 1

2019 ◽  
Vol 37 (32) ◽  
pp. 3050-3058 ◽  
Author(s):  
Smita Bhatia ◽  
Yanjun Chen ◽  
F. Lennie Wong ◽  
Lindsey Hageman ◽  
Kandice Smith ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Primary Tumor ◽  
Alkylating Agents ◽  
Neurofibromatosis Type ◽  
Childhood Cancer Survivors ◽  
University Of Alabama ◽  
Primary Tumors ◽  
Increased Risk ◽  
Childhood Cancer Survivor Study

PURPOSE Fundamental gaps in knowledge regarding the risk of subsequent neoplasms (SNs) in children with pathogenic neurofibromatosis type 1 (NF1) variants exposed to radiation and/or alkylator chemotherapy have limited the use of these agents. METHODS We addressed these gaps by determining the SN risk in 167 NF1-affected versus 1,541 non–NF1-affected 5-year childhood cancer survivors from the Childhood Cancer Survivor Study and 176 nonoverlapping NF1-affected individuals with primary tumors from University of Alabama at Birmingham and Children’s Hospital of Philadelphia exposed to radiation and/or chemotherapy. Proportional subdistribution hazards multivariable regression analysis was used to examine risk factors, adjusting for type and age at primary tumor diagnosis and therapeutic exposures. RESULTS In the Childhood Cancer Survivor Study cohort, the 20-year cumulative incidence of SNs in NF1 childhood cancer survivors was 7.3%, compared with 2.9% in the non-NF1 childhood cancer survivors ( P = .003), yielding a 2.4-fold higher risk of SN (95% CI, 1.3 to 4.3; P = .005) in the NF1-affected individuals. In the University of Alabama at Birmingham and Children’s Hospital of Philadelphia cohort, among NF1-affected individuals with a primary tumor, the risk of SNs was 2.8-fold higher in patients with irradiated NF1 (95% CI, 1.3 to 6.0; P = .009). In contrast, the risk of SNs was not significantly elevated after exposure to alkylating agents (hazard ratio, 1.27; 95% CI, 0.3 to 3.0; P = .9). CONCLUSION Children with NF1 who develop a primary tumor are at increased risk of SN when compared with non-NF1 childhood cancer survivors. Among NF1-affected children with a primary tumor, therapeutic radiation, but not alkylating agents, confer an increased risk of SNs. These findings can inform evidence-based clinical management of primary tumors in NF1-affected children.

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