scholarly journals Effect of Genetic Variation in CYP450 on Gonadal Impairment in a European Cohort of Female Childhood Cancer Survivors, Based on a Candidate Gene Approach: Results from the PanCareLIFE Study

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4598
Author(s):  
M. Perk ◽  
Linda Broer ◽  
Yutaka Yasui ◽  
Leslie Robison ◽  
Melissa Hudson ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Ovarian Function ◽  
Meta Analysis ◽  
Alkylating Agents ◽  
Childhood Cancer Survivors ◽  
P Value ◽  
Candidate Gene Approach ◽  
Gonadal Dysfunction ◽  
The Impact

Background: Female childhood cancer survivors (CCSs) carry a risk of therapy-related gonadal dysfunction. Alkylating agents (AA) are well-established risk factors, yet inter-individual variability in ovarian function is observed. Polymorphisms in CYP450 enzymes may explain this variability in AA-induced ovarian damage. We aimed to evaluate associations between previously identified genetic polymorphisms in CYP450 enzymes and AA-related ovarian function among adult CCSs. Methods: Anti-Müllerian hormone (AMH) levels served as a proxy for ovarian function in a discovery cohort of adult female CCSs, from the pan-European PanCareLIFE cohort (n = 743; age (years): median 25.8, interquartile range (IQR) 22.1–30.6). Using two additive genetic models in linear and logistic regression, nine genetic variants in three CYP450 enzymes were analyzed in relation to cyclophosphamide equivalent dose (CED) score and their impact on AMH levels. The main model evaluated the effect of the variant on AMH and the interaction model evaluated the modifying effect of the variant on the impact of CED score on log-transformed AMH levels. Results were validated, and meta-analysis performed, using the USA-based St. Jude Lifetime Cohort (n = 391; age (years): median 31.3, IQR 26.6–37.4). Results: CYP3A4*3 was significantly associated with AMH levels in the discovery and replication cohort. Meta-analysis revealed a significant main deleterious effect (Beta (95% CI): −0.706 (−1.11–−0.298), p-value = 7 × 10−4) of CYP3A4*3 (rs4986910) on log-transformed AMH levels. CYP2B6*2 (rs8192709) showed a significant protective interaction effect (Beta (95% CI): 0.527 (0.126–0.928), p-value = 0.01) on log-transformed AMH levels in CCSs receiving more than 8000 mg/m2 CED. Conclusions: Female CCSs CYP3A4*3 carriers had significantly lower AMH levels, and CYP2B6*2 may have a protective effect on AMH levels. Identification of risk-contributing variants may improve individualized counselling regarding the treatment-related risk of infertility and fertility preservation options.

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.

The Association of Mitochondrial Copy Number with Sarcopenia in Adult Survivors of Childhood Cancer

2021 ◽  
Author(s):  
Kelly McCastlain ◽  
Carrie R Howell ◽  
Catherine E Welsh ◽  
Zhaoming Wang ◽  
Carmen L Wilson ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Childhood Cancer ◽  
Muscle Mass ◽  
Copy Number ◽  
Statistical Tests ◽  
Quantitative Polymerase Chain Reaction ◽  
Alkylating Agents ◽  
Childhood Cancer Survivors ◽  
Central Nervous System Tumor ◽  
Mitochondrial Dna Copy Number

Abstract Background Adult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood (PB) mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors. Methods Among 1,762 adult childhood cancer survivors (51.6% male; median age = 29.4 [IQR = 23.3-36.8] years), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided. Results The prevalence of sarcopenia was 27.0%, higher among females than males (31.5% vs. 22.9%; P < 0.001) and associated with age at diagnosis; 51.7% of survivors with sarcopenia were diagnosed ages 4-13 years (p = 0.01). Sarcopenia was most prevalent (39.0%) among central nervous system tumor survivors. Cranial radiation (OR = 1.84; 95% CI = 1.32-2.59) and alkylating agents (OR = 1.34; 95% CI = 1.04-1.72) increased, while glucocorticoids decreased odds (OR = 0.72; 95% CI = 0.56-0.93) of sarcopenia. mtDNAcn decreased with age (β=-0.81; P = 0.002), was higher among females (β = 9.23; P = 0.01) and among survivors with a C allele at mt.204 (β=-17.9; P = 0.02). In adjusted models, every standard deviation decrease in mtDNAcn increased the odds of sarcopenia 20% (OR = 1.20; 95% CI = 1.07-1.34). Conclusions While a growing body of evidence supports PB mtDNAcn as a biomarker for adverse health outcomes, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.

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.

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 Exercise Interventions and Cardiovascular Health in Childhood Cancer: A Meta-analysis

2020 ◽  
Vol 41 (03) ◽  
pp. 141-153 ◽  
Author(s):  
Javier S. Morales ◽  
Pedro L. Valenzuela ◽  
Alba M. Herrera-Olivares ◽  
Antonio Baño-Rodrigo ◽  
Adrián Castillo-García ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Meta Analysis ◽  
Childhood Cancer Survivors ◽  
Left Ventricular ◽  
Mean Difference ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Exercise Interventions

AbstractThis study analyzed the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors. Relevant articles were systematically searched in PubMed, CINAHL, and Web of Science databases (since inception to 11th September 2019). We performed a meta-analysis (random effects) to determine the mean difference (expressed together with 95% confidence intervals) between pre- and post-intervention values for those cardiovascular endpoints reported in more than three studies. Twenty-seven studies (of which 16 were controlled studies) comprising 697 participants were included. Only three studies reported adverse events related to exercise interventions. Exercise resulted in an increased performance on the 6-minute walk distance test (mean difference=111 m, 95% confidence interval=39–183, p=0.003) and a non-significant trend (mean difference=1.97 ml∙kg−1∙min−1, 95% confidence interval=−0.12–4.06, p=0.065) for improvement in peak oxygen uptake. Furthermore, left ventricular ejection fraction was preserved after exercise interventions (mean difference=0.29%, 95% confidence interval=−1.41–1.99, p=0.738). In summary, exercise interventions might exert a cardioprotective effect in childhood cancer survivors by improving – or attenuating the decline of – physical capacity and cardiovascular function. Further studies, particularly randomized controlled trials, are needed to confirm these benefits.

Meta-analysis of second cancer risk after radiotherapy among childhood cancer survivors

2011 ◽  
Vol 146 (1-3) ◽  
pp. 263-267 ◽  
Author(s):  
K. Doi ◽  
M. N. Mieno ◽  
Y. Shimada ◽  
H. Yonehara ◽  
S. Yoshinaga
Keyword(s):  
Cancer Risk ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Meta Analysis ◽  
Childhood Cancer Survivors ◽  
Second Cancer ◽  
Second Cancer Risk

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.

Smoking, Binge Drinking, and Drug Use Among Childhood Cancer Survivors: A Meta-Analysis

2016 ◽  
Vol 63 (7) ◽  
pp. 1254-1263 ◽  
Author(s):  
Stacey Marjerrison ◽  
Eleanor Hendershot ◽  
Brianna Empringham ◽  
Paul C. Nathan
Keyword(s):  
Drug Use ◽  
Cancer Survivors ◽  
Childhood Cancer ◽  
Binge Drinking ◽  
Meta Analysis ◽  
Childhood Cancer Survivors
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