Causes Of Childhood Cancer Research Articles

Perceptions and attitudes about the contribution of the environment to childhood cancer: a pilot study in a medical guild and undergraduate students

BackgroundIdentifying and recognizing environmental risk factors for childhood cancer is crucial to prevent it. Medical guild are the first contact to monitor children’s health. Therefore, courses about the contribution of chemical toxins in the environment and health outcomes such as cancer should be included in their professional training. This study aimed to evaluate the perceptions and attitudes of a medical guild and undergraduate students in health sciences about the contribution of the environment to childhood cancer.MethodsA pilot study was conducted, an online survey including thirteen questions was shared among medical guild members and undergraduate students in health sciences. Frequencies, percentages, and chi-square homogeneity tests were calculated to compare groups.ResultsGenetic factors ranked as the first possible cause of childhood cancer (88.2% medical guild and 97.7% undergraduate students). However, 70.6% of medical guild and 64.6% of undergraduate students reported that they have ever suspected that childhood cancer could be related to the environmental conditions in which children live. More than 95% of the participants reported that they would find it useful to have more knowledge about environmental risks and cancer. When data were analyzed by profession (medical guild) and academic year (undergraduate students), no significant differences were observed. Nonetheless, comparisons by academic discipline between undergraduate students, showed that a higher percentage of medicine and environmental sciences and health (over 98%) reported environmental exposure as risk factors associated with childhood cancer compared to 75% from physiotherapy, (p = 0.001).ConclusionsIn this study, the environmental contribution to childhood cancer is not clear among the medical guild and undergraduate students. They should be trained on the topic of cancer and the environment.

Exploring the potential of IL-10 for risk assessment and early intervention in pediatric ALL

Acute lymphoblastic leukemia (ALL), a leading cause of childhood cancer, targets immune system B and T cells. While understanding its causes is crucial, predicting susceptibility holds immense power for early diagnosis and intervention. This study explored the potential of interleukin 10 (IL-10), a key immune regulator, as a predictive tool in Egyptian children. Investigating 100 ALL patients and 100 healthy controls, we analyzed the IL10 gene polymorphism (-1082 A/G) and serum levels. Strikingly, both the G allele and higher serum IL-10 levels were significantly associated with increased ALL risk (p < 0.05, OR > 1). Moreover, IL-10 emerged as a remarkably accurate predictor, boasting an AUC of 0.995, with a sensitivity of 97% and specificity of 96%. These findings unveil the potential of IL-10 as a powerful predictive tool for pediatric ALL in the studied Egyptian population. Identifying individuals with the GG/AG haplotype and elevated IL-10 levels could enable early intervention and potentially improve outcomes. While further validation in larger and more diverse populations is needed, this study paves the way for personalized risk assessment and potentially revolutionizes how we combat this childhood killer.

Polygenic Pharmacogenomic Markers as Predictors of Toxicity Phenotypes in the Treatment of Acute Lymphoblastic Leukemia: A Single-Center Study.

Acute lymphoblastic leukemia (ALL) is the most prevalent cause of childhood cancer and requires a long course of therapy consisting of three primary phases with interval intensification blocks. Although these phases are necessary to achieve remission, the primary chemotherapeutic agents have potentially serious toxicities, which may lead to delays or discontinuations of therapy. The purpose of this study was to perform a comprehensive pharmacogenomic evaluation of common antileukemic agents and develop a polygenic toxicity risk score predictive of the most common toxicities observed during ALL treatment. This cross-sectional study included 75 patients with pediatric ALL treated between 2012 and 2020 at the University of Florida. Toxicity data were collected within 100 days of initiation of therapy using CTCAE v4.0 for toxicity grading. For pharmacogenomic evaluation, single-nucleotide polymorphisms (SNPs) and genes were selected from previous reports or PharmGKB database. 116 unique SNPs were evaluated for incidence of various toxicities. A multivariable multi-SNP modeling for up to 3-SNP combination was performed to develop a polygenic toxicity risk score of prognostic value. We identified several SNPs predictive of toxicity phenotypes in univariate analysis. Further multivariable SNP-SNP combination analysis suggest that susceptibility to chemotherapy-induced toxicities is likely multigenic in nature. For 3-SNPscore models, patients with high scores experienced increased risk of GI (P = 2.07E-05, 3 SNPs: TYMS-rs151264360/FPGS-rs1544105/GSTM1-GSTM5-rs3754446), neurologic (P = .0005, 3 SNPs: DCTD-rs6829021/SLC28A3-rs17343066/CTPS1-rs12067645), endocrine (P = 4.77E-08, 3 SNPs: AKR1C3-rs1937840/TYMS-rs2853539/CTH-rs648743), and heme toxicities (P = .053, 3 SNPs: CYP3A5-rs776746/ABCB1-rs4148737/CTPS1-rs12067645). Our results imply that instead of a single-SNP approach, SNP-SNP combinations in multiple genes in drug pathways increases the robustness of prediction of toxicity. These results further provide promising SNP models that can help establish clinically relevant biomarkers allowing for greater individualization of cancer therapy to maximize efficacy and minimize toxicity for each patient.

Comparison of goal-directed and standard therapy for hemodynamic management in heart transplantation surgery

Neuroblastoma is the most common solid extracranial tumor in childhood, that arises from neural crest cells. The cervical location is the least frequent and its clinical manifestations are diverse, from cervical mass, dyspnea, stridor, Horner's syndrome or dysphagia. In this case report, we present a male infant with an atypical clinical symptoms, with upper airway obstruction that can occur in multiple contexts, whether malformative or neoplastic masses; Simple and contrast-enhanced neck tomography revealed a lesion in the right posterior cervical triangle with involvement in the retropharyngeal region and significant displacement of the airway. The tumor was successfully excised. The histopathological diagnosis was mixed ganglioneuroblastoma, rich in Schwannian stroma, treatment was started with the COG protocol with 4 cycles of chemotherapy, at the end a control MRI was performed without evidence of tumor recurrence. The importance of recognizing primary tumors with atypical signs and symptoms is highlighted, given that the frequency of neuroblastomas, statistically speaking, is the second cause of childhood cancer, early diagnosis must be made in order to achieve successful treatment.

DDDR-10. INHIBITING INSULIN SIGNALING REVERSES RESISTANCE TO PI3K-MTOR INHIBITORS IN AGGRESSIVE PEDIATRIC HIGH-GRADE GLIOMAS

Abstract Primary central nervous system (CNS) tumors are now the most common cause of childhood cancer–related deaths. Pediatric high-grade gliomas (pHGGs) are among the most lethal brain tumors with a 5-year survival rate of only 20%. MYCN pHGGs represent one subgroup with an unmet need for therapeutics. MYCN belongs to the family of MYC transcription factors that regulate numerous cancer hallmarks such as proliferation, apoptosis, and metabolism. While no direct inhibitors of MYCN are in clinical trial, current strategies focus on targeting the MYCN mediated transcriptional machinery or cell cycle regulators. Lack of relevant pHGG models for pre-clinical testing contribute to limited therapeutic efficacy. To address these knowledge gaps, we developed a novel mouse model of MYCN pHGG using the FLEx-Cre switch system, whereby neural stem cells are selectively delivered with MYCN cDNA and shRNA targeting the tumor suppressor genes p53 and Pten and form tumors in vivo. We identified that this model harbors hyper-activation of the PI3K/AKT/mTOR signaling pathway. We demonstrate that dual PI3K-mTOR blood brain barrier penetrant inhibitors are effective in reducing pHGG growth and MYCN protein levels. Because treatment-resistance is a fundamental feature of pHGGs, we developed a novel drug-resistance model of MYCN pHGG as a mechanistic tool to identify relevant resistance mechanisms. Using transcriptome analysis, we identified the insulin growth factor signaling pathway as our top mechanism of resistance. We hypothesized that MYCN is a critical driver of pHGG and can be effectively targeted via dual inhibition of PI3K-mTOR and IGF/Insulin signaling pathways. We tested next generation inhibitors of IGF and PI3K/mTOR pathways and performed genetic and pharmacological assays in our MYCN pHGG and human MYCN pHGG cells. Inhibition of both pathways in our MYCN pHGG model and human MYCN cells were synergistic, leading to significant decreases in cell growth and MYCN signaling.

Development of Culturally Adapted Media to Increase Community Awareness of Childhood Cancer in Tanzania

PURPOSE There is low childhood cancer awareness in many low and middle income countries (LMICs), contributing to delayed hospital presentation, and treatment abandonment. In Tanzania, only 20% of the estimated 3,500 new cases per year present for treatment. While childhood cancer awareness media exist, they are not adapted for use in many LMIC communities, including Tanzania. METHODS To reach consensus on childhood cancer education content and education strategy selection, a Delphi process was completed with an expert advisory panel representing three Tanzanian referral hospitals. Focus groups discussions (FGD) were completed with rural and urban communities from each of the Mwanza, Dar Es Salaam and Kilimanjaro regions. Thematic analysis was guided by content consensus to identify community knowledge gaps. Sample education materials were reviewed to identify preferred delivery format. RESULTS A total of 14 and 72 participants formed the expert panel and community FGD respectively. Education strategies with the highest feasibility and impact included community health worker led education, a song, and social media messaging. The following key knowledge content areas were identified to have the lowest community awareness. (1) The cause of most childhood cancer is unknown: 83% felt untreated illnesses, cooking oil, witchcraft, immune system deficiency, and the environment were causes of childhood cancer; (2) Symptom recognition and hospital based studies can improve early detection: 66% reported that ill children see a traditional healer or pharmacist and only go a hospital if febrile or if symptoms do not improve; (3) Most childhood cancer can be cured with early detection: 50% felt that there is no cure. CONCLUSION This study identified key childhood cancer knowledge gaps within the Tanzanian community and culturally adapted strategies to disseminate education media. Additional studies are needed to evaluate the impact of culturally adapted media on community awareness and early hospital presentation in the region.

Identification of candidate genes in a family with cancer overload by whole-exome sequencing.

Approximately 120 out of every 1 million children in the world develop cancer each year. In Turkey, 2500-3000 children are diagnosed with new cancer each year. The causes of childhood cancer have been studied for many years. It is known that many cancers in children, as in adults, cause uncontrolled cell growth, and develop as a result of mutations in genes that cause cancer. The investigation of family history within this context in the study, a total of 13 individuals consisting of all children and adults in the family were examined using the whole-exome sequencing (WES) with the individuals who were diagnosed with cancer in the family, who were detected to have different cancer profiles, and defined as high risk and to determine the gene or genes through which the disease has developed. At the end of the study, a total of 30 variants with a pathogenic record in the family were identified. A total of 10 pathogenic variants belonging to 8 different genes from these variants have been associated with various cancer risks. A significant scientific contribution has been made to the mechanism of disease formation by studying a family with a high cancer burden and by finding the genes associated with the disease. In addition, by the results obtained, family members with cancer predisposition were selected after a risk analysis conducted in this family, and the necessary examinations and scans were recommended to provide an early diagnostic advantage.

High-grade gliomas in children and adolescents: is there a role for reoperation?

Tumors of the CNS are the main causes of childhood cancer and have an incidence that exceeds that of leukemia. In addition, they are the leading causes of cancer-related death in childhood. High-grade gliomas account for 11% of such neoplasms and are characterized by aggressive clinical behavior and high morbidity and mortality. There is a lack of studies focusing on the factors that can prolong survival in these patients or guide therapeutic interventions. The authors aimed to investigate the factors related to longer survival durations, with a focus on reoperation for gross-total resection (GTR). In this retrospective cohort study, the authors analyzed 78 patients diagnosed with high-grade gliomas occurring across all CNS locations except diffuse intrinsic pontine gliomas. Patients 0 to < 19 years of age were followed up at the Pediatric Oncology Institute. Overall survival (OS) and progression-free survival (PFS) were analyzed in the context of various prognostic factors, such as age, sex, histology, extent of tumor resection, reoperation for GTR, adjuvant treatment, and treatment initiation from 2010 onward. With a mean age at diagnosis of 8.7 years, 50% of the patients were female and approximately 39% underwent GTR at some point, which was already achieved in approximately 46% of them in the first surgery. The median OS was 17 months, and PFS was 10 months. In terms of median OS, the authors found no significant difference between those with reoperation for GTR and patients without GTR during treatment. Significant differences were observed in the OS in terms of the extent of resection in the first surgery, age, sex, Ki-67 expression, adjuvant treatment, and treatment initiation from 2010 onward. Furthermore, the PFS values significantly differed between those with GTR in the first surgery and Ki-67 expression ≥ 50%. This study demonstrates the importance of GTR for these neoplasms, highlights the role of surgeons in its achievement in the first attempt, and questions the role of reoperation for this purpose. Finally, this study further supports the use of combined adjuvant treatment for the improvement of OS and PFS.

Parental occupational organic dust exposure and selected childhood cancers in Denmark 1968–2016

BackgroundParental occupational exposures are suggested as contributing causes of childhood cancer. MethodsChildren age< = 19, born in Denmark and diagnosed with leukemia, central nervous system (CNS) cancers and likely prenatally initiated cancers [hepatoblastoma, medulloblastoma, Wilms tumor (nephroblastoma), neuroblastoma, retinoblastoma and acute lymphoid leukemia] n = 4268 were identified using Danish registries. We randomly selected twenty-five controls per case matched on birth year and sex. Parents and their employment histories were extracted from nationwide registries. We examined occupational dust exposures perinatally and postnatally in both parents. Odds ratios (ORs) and 95 % confidence intervals (95 % CI) were estimated using conditional logistic regression. ResultsMaternal wood dust exposure from birth to diagnosis was associated with increased risks of leukemia (OR 1.44, 95 % CI 1.08–1.94) and acute myeloid leukemia (OR 2.14, 95 % CI 1.13–4.03); exposure to paper dust was associated with CNS cancer (OR 2.28, 95 % CI 1.22–4.2).. Paternal exposure to wood dust was associated with astrocytoma in both periods (OR 1.43, 95 % CI 1.05–1.96 and 1.42, 1.09–1.86, respectively) and CNS cancer (OR 1.24, 95 % CI 1.00–1.53) in the perinatal period. The increased risk observed for potentially prenatally-initiated cancers in relation to wood was driven by ORs for neuroblastoma (1.54, 95 % CI 1.03–2.29) and hepatoblastoma (2.41, 95 % CI 0.99–5.88). An OR of 2.58 (95 % CI 1.10–6.05) for CNS cancer was associated with both parents working in textile industries postnatally. ConclusionThe study suggests that parental exposure to wood dust may increase risk of specific childhood cancers.

Challenges of screening germline predispositions in children

Genetic predisposition is a major cause of childhood cancer. Multiple cancer-predisposing syndromes have been identified, including Li-Fraumeni syndrome (LFS), neurofibromatosis type 1, APC-related adenomatous polyposis, Beckwith-Wiedemann syndrome, multiple endocrine neoplasia 1, ataxia telangiectasia, RUNX1 deficiency, Fanconi anemia, Bloom syndrome, and PTEN hamartoma tumor syndrome. LFS is a prototypical genetically predisposing condition. Accordingly, individualized therapy, surveillance, risk reduction, and family counseling are needed when a patient is diagnosed with LFS. More ethically important problems are encountered in a pediatric LFS patient, including the identification of patients requiring screening, the age at screening, the process of obtaining informed consent from children, and the responsibility of following a pediatric patient with a genetic predisposition. Therefore, it is crucial to determine whether planned genetic testing has direct benefits for pediatric patients. In this context, TP53 testing may be justified in a pediatric cancer patient with suspected LFS, given the importance of decisions such as the use of radiotherapy and the screening of family members as hematopoietic stem cell transplantation donors, the surveillance of subsequent cancers, and counseling for family members. In this review article, I have discussed these issues and indicated some consensus among various clinicians, including adult hematologists.

‘Why us?’ Causal attributions of childhood cancer survivors, survivors’ parents and community comparisons - a mixed methods analysis

Introduction: Understanding the cause of their cancer is important for many cancer patients. Childhood cancer survivors’/survivors’ parents’ beliefs about cancer etiology are understudied. We aimed to assess survivors’/parents’ beliefs about what causes childhood cancer, compared with beliefs in the community. We also investigated the influence of clinical and socio-demographic characteristics on the participants’ beliefs about cancer etiology.Methods: This two-stage study investigated the participants’ beliefs, by using questionnaires assessing causal attributions related to childhood cancer (stage 1) and then undertaking telephone interviews (stage 2; survivors/survivors’ parents only) to get an in-depth understanding of survivors’/survivors’ parents beliefs. We computed multivariable regressions to identify factors associated with the most commonly endorsed attributions: bad luck/chance, environmental factors and genetics. We analyzed interviews using thematic analysis.Results: Six hundred one individuals (64.6% survivors and 35.4% survivors’ parents) and 510 community comparisons (53.1% community adults, 46.9% community parents) completed the question on causal attributions. We conducted 87 in-depth interviews. Survivors/survivors’ parents (73.9%) were more likely to believe that chance/bad luck caused childhood cancer than community participants (42.4%). Community participants more frequently endorsed that genetics (75.3%) and environmental factors (65.3%) played a major role in childhood cancer etiology (versus survivors’ and survivors’ parents: genetics 20.6%, environmental factors: 19.3%). Community participants, participants with a first language other than English, and reporting a lower quality of life were less likely to attribute bad luck as a cause of childhood cancer. Community participants, all participants with a higher income and higher education were more likely to attribute childhood cancer etiology to environmental factors.Conclusion: Causal attributions differed between survivors/survivors’ parents and community participants. Most of the parents and survivors seem to understand that there is nothing they have done to cause the cancer. Understanding survivors’ and survivors’ parents’ causal attributions may be crucial to address misconceptions, offer access to services and to adapt current and future health behaviors.

The Iceberg Map of germline mutations in childhood cancer: focus on primary immunodeficiencies.

The risk of cancer is higher, and its outcome is worse in patients with primary immunodeficiency (PID) than in members of the general population. Thus, the inter-relationship of malignant diseases with PIDs requires more study. Large genetic screens identified a vast number of germline mutations in childhood cancer patient samples. Although TP53 was the most frequent single gene identified as mutated, many PID disorders like DNA repair defects are among the inborn causes of childhood cancer. We provide a comprehensive analysis of compiled data from seven recent studies that focused on germline genetic landscapes and preexisting conditions in pediatric oncology. As potentially causal germline variants were identified in ≈8% of malignancies in children and adolescents, we visualized this proportion as the 'tips of the icebergs'. The results of additional network analyses showed the shared patterns of germline mutations in various malignancies and yielded a spatial distribution of the 'icebergs'. The 'iceberg map of germline mutations in childhood cancers' was created to increase the awareness of the inborn genetic underpinnings of childhood malignancies and their relationships with immunodeficiencies. Needs and perspectives of clinical immunologists and pediatric oncologists to both improve patient care and guide research at this critical interface are discussed. VIDEO ABSTRACT.

Childhood cancer research in oxford III: The work of CCRG on ionising radiation

BackgroundHigh doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topicMethodsMost UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling.ResultsThis paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975–2014.ConclusionThe work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group’s work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

Advancing Parental Age and Risk of Solid Tumors in Children: A Case-Control Study in Peru.

Background The causes of childhood cancer are not well known, but the advanced age of the parents has been suggested as a risk factor for childhood cancer in several observational studies. In this study, we examine a possible link between parental age and childhood solid tumors. Methods We conducted a hospital-based case-control study (310 cases and 620 controls, matched by age and gender) at Rebagliati Hospital, Lima, Peru. Odd ratio was used to compare categories of advancing maternal and paternal age with and without adjusting for possible confounding factors were calculated. Results The risk of childhood retinoblastoma was significantly higher among children of mothers aged> 35 years (adjusted OR 1.21; 95% CI, 1.09-6.08) and fathers aged> 35 years (OR 1.17; 1.01-16.33). A significant trend with increasing mother's age (p = 0.037) and father's age (p = 0.005) was found. There were more risks to development of non-Hodgkin's lymphoma (p = 0.047) and gonadal germ cell tumors (p = 0.04) for advanced paternal age. There was a strong protective effect of increasing parity on risk of solid tumors in children (p=0.0015). Conclusion Our results suggest that advanced parental age is associated with the risk for the development of retinoblastoma. Advanced paternal age increases the risk of non-Hodgkin lymphoma and gonadal germ cell tumor. The higher the order of birth of the children, the less the chance of developing any neoplasm.

The influence of prenatal exposure to trans-fatty acids for development of childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and a case-control study

BackgroundLittle is known about the causes of childhood cancer, partly as not many children develop cancer, although childhood cancer is a leading cause of death by disease in the young. The young age of the children suggests that risk factors for childhood cancer may be present during pregnancy. Previous studies have shown that exposure to trans-fat, a type of unsaturated fat common in industrially produced foods (iTFA), has adverse health effects in adults, including the risk of developing cancer. Haematopoietic neoplasms are the most common cancer types among European children under the age of 15 years. This study will bring new knowledge as to whether trans-fat and other fatty acids may also increase the risk of developing haematopoietic neoplasms during childhood.MethodsWe will investigate if the Danish iTFA legislation ban, which radically reduced the use of iTFA in foodstuffs, influenced the risk of childhood haematopoietic neoplasms in children born either before or after the change in legislation, adjusting for relevant secular trends. Further, in a case-control study, we will examine if levels of fatty acids in dried blood spots from newborns can predict the risk of developing childhood haematopoietic neoplasms. Permission from the Danish Data Protection Agency and the Ethical Committee has been granted.DiscussionThe results from this study will provide important information about fatty acids in the mother’s diet as a contributor to development of haematopoietic neoplasms during childhood, which may result in relevant preventive action.Trial registrationNot relevant.

Can Big Data Shed Light on the Origins of Pediatric Cancer?

* Abbreviations: AML — : acute myelogenous leukemia aOR — : adjusted odds ratio CI — : confidence interval CLIPS — : California Late Impact of Phototherapy Study ICD-9 — : International Classification of Diseases, Ninth Revision LIGHT — : Late Impact of Getting Hyperbilirubinemia or Phototherapy Twenty-five years ago, Sir Richard Doll and Sir Richard Peto estimated in their landmark monograph, The Causes of Cancer , that 75% to 80% of adult cancer could be attributed to lifestyle choices and environmental exposures.1 In stark contrast, elucidating the causes of childhood cancer remains one of the most vexing questions in medicine. Despite progress in identifying the molecular causes of many pediatric tumors, whether there are extrinsic environmental causes of pediatric cancer remains an elusive question. Without this evidence, the “primary” prevention of childhood cancer remains out of reach. The inherent epidemiologic challenge of studying the etiology of childhood cancer is simple math. Childhood cancer is a rare event, and the power to detect an association is limited by the small number of incident cases. In this issue of Pediatrics , 2 companion articles by the same set of authors address this conundrum of rarity by using “Big Data” to address whether neonatal phototherapy can be implicated as a cause of childhood cancer. Wickremasinghe et al2 report the results of the California Late Impact of Phototherapy Study (CLIPS), a study of ∼5 million infants who were identified by the California Office of Statewide Health Planning and Development by probabilistically linking vital statistics (birth and death certificates) with patient discharge data between 1998 and 2007. A total of 1100 infants (58 of whom had received phototherapy) developed cancer between 60 to 365 days of life. Because there are many factors previously identified that increase the risk of hyperbilirubinemia that might independently also affect cancer risk and thereby confound the association between phototherapy and infant cancer, the authors developed a “score” for each subject that captured all the reasons known to increase the need/propensity for phototherapy. This propensity score was necessary because it would not have been possible … Address correspondence to A. Lindsay Frazier, MD, ScM, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215. E-mail: lindsay_frazier{at}dfci.harvard.edu

Children with Cancer: A Comprehensive Reference Guide for Parents

Children with Cancer: A Comprehensive Reference Guide for Parents: A Comprehensive Reference Guide for Parents provides invaluable information to help families dealing with a child who has cancer. Medical and psychological aspects of childhood cancer are addressed, and the author provides many tips on helping children through the entire process of diagnosis and treatment. Equally important, the book includes resources to help families to cope with the emotional difficulties that may arise. The format of the book works very well, with sections on the different types of childhood cancers, treatments that are currently offered, and advice on coping with various medical conditions. The introductory chapter addresses the main concerns that most parents and families have: identifying the types of cancer that affect children and learning about the causes of childhood cancer. Each type of cancer has sections that include information on symptoms, rate of incidence, diagnosis, treatment, complications, and prognosis. The author is the parent of a child with a solid tumor cancer. Her child is a long-term survivor, and the book includes a chapter on childhood cancer survivors, including information on rehabilitation, chemotherapy drugs, radiation, and side effects. The book also includes a chapter that addresses the possibility of a child's death. Vitally important subjects concerning pain management and palliative care are extensively covered. Also, there are chapters that address the subject of how to deal with the feelings of siblings and adolescent cancer patients. This book's author is a retired reference librarian, which is evidenced by the excellent references included in the many bibliographies and appendixes. There is information on clinical trials that concern childhood cancer therapy, as well as pediatric hospitals and other organizations that belong to the Children's Oncology Group (COG), both in the United States and internationally. Explanations of medical tests used for diagnosing and treating childhood cancer, and a medical glossary are also featured. It would be beneficial to have a yearly updated edition of Children with Cancer because pediatric oncology research discovers new treatments frequently. A number of print and online sources in the “Further Resources” sections and chapters would need to be updated often. But this book still serves as an invaluable resource for the parent of a child with cancer, because the author manages to comb through all of the information that is increasingly available online. It is an excellent addition to any health sciences library but is an essential part of the collection of pediatric hospital libraries.

Effect of Environmental Exposures and Diet on Genotoxicity in Newborns and Pregnant Mothers in Crete (RHEA Mother-Child Cohort)

Effect of Environmental Exposures and Diet on Genotoxicity in Newborns and Pregnant Mothers in Crete (RHEA Mother-Child Cohort)Abstract Number:2109 Cristina O'Callaghan-Gordo*, Eleni Fthenou, Marie Pedersen, Leda Chatzi, Ana Espinosa, Marina Vafeiadi, Euripides Stephanou, Hannu Kiviranta, Marie Vahter, Rob Beelen, Mark Nieuwenhuijsen, Jos Kleinjans, Micheline Kirsch-Volders, and Manolis Kogevinas Cristina O'Callaghan-Gordo* Centre for Research in Environmental Epidemiology (CREAL), Spain, E-mail Address: [email protected] Search for more papers by this author , Eleni Fthenou Faculty of Medicine, University of Crete (UoC), Greece, E-mail Address: [email protected] Search for more papers by this author , Marie Pedersen Centre for Research in Environmental Epidemiology (CREAL), Spain, E-mail Address: [email protected] Search for more papers by this author , Leda Chatzi Faculty of Medicine, University of Crete (UoC), Greece, E-mail Address: [email protected] Search for more papers by this author , Ana Espinosa Centre for Research in Environmental Epidemiology (CREAL), Spain, E-mail Address: [email protected] Search for more papers by this author , Marina Vafeiadi Faculty of Medicine, University of Crete (UoC), Greece, E-mail Address: [email protected] Search for more papers by this author , Euripides Stephanou School of Sciences and Engineering, University of Crete (UoC), Greece, E-mail Address: [email protected] Search for more papers by this author , Hannu Kiviranta Department of Environmental Health, National Institute for Health and Welfare, Finland, E-mail Address: [email protected] Search for more papers by this author , Marie Vahter Department of Environmental Medicine, Karolinska Institute, Sweden, E-mail Address: [email protected] Search for more papers by this author , Rob Beelen Institute for Risk Assessment Sciences, Division Environmental Epidemiology, Utrecht University, Netherlands, E-mail Address: [email protected] Search for more papers by this author , Mark Nieuwenhuijsen Centre for Research in Environmental Epidemiology (CREAL), Spain, E-mail Address: [email protected] Search for more papers by this author , Jos Kleinjans Department of Toxicogenomics, Maastricht University, Netherlands, E-mail Address: [email protected] Search for more papers by this author , Micheline Kirsch-Volders Laboratory of Cell Genetics, Faculty of Science and Bio-engineering, Vrije Universitei Brussel, Belgium, E-mail Address: [email protected] Search for more papers by this author , and Manolis Kogevinas Centre for Research in Environmental Epidemiology (CREAL), Spain, E-mail Address: [email protected] Search for more papers by this author AbstractBackground: Incidence of childhood cancer has increased in recent decades. The causes of childhood cancer are poorly understood. High micronuclei (MN) frequency has been associated in adults with future cancer risk. Aim: We examined MN frequency, a biomarker of early genetic effects, in cord and mother’s blood in relation to environmental exposures and diet during pregnancy in the RHEA mother-child cohort in Crete, Greece (part of the European NewGeneris study).Methods: The cytokinesis-block micronucleus assay was used to assess MN frequencies in bi- and mono-nucleated T-lymphocytes in 223 newborns and 214 mothers in 2007-08. Persistent organic pollutants, metals (Cd, Pb) and cotinine were measured in mothers and adducts of genotoxic compounds were available from newborns. The ESCAPE methods were used for modeling outdoor air pollution at home addresses in 2010. Associations between exposures and MN frequency were examined using negative binomial regression.Results: Exposure to air pollutants during whole pregnancy was not associated with increased MN frequency in newborns. In mothers increased risk of MN frequency in bi-nucleated cells was found for PM2.5 (adjusted IRR per 5µg/m3 =1.6, 95%CI=1.1-2.5). Increased MN frequency in newborns and mothers was associated with season of birth with highest risk in summer (newborns: adjusted IRR =2.1 95%CI=1.6-2.8; mothers: adjusted IRR=1.5, 95%CI=1.1-2.0). Increased MN frequency in bi-nucleated cells was observed among large birth weight (>4000g) newborns (adjusted IRR =1.3, 95%CI=1.0-1.8). There were no consistent patterns in MN frequency and other environmental contaminants or active/passive smoking. Some associations were found between meat, vegetables, fruit and iron supplements intake during pregnancy and MN frequency in bi- and mono-nucleated cells in newborns and mothers.Conclusions: We found few and not fully consistent patterns of genotoxicity risks in newborns associated with environmental and dietary exposures.

Children's Oncology Group's 2013 blueprint for research: Epidemiology

Investigators worldwide have for over 40 years conducted case-control studies aimed at determining the causes of childhood cancer. The central challenge to conducting such research is the rarity of childhood cancer, thus many studies aggregate cases through clinical trials organizations such as COG. Rarity also precludes the use of prospective study designs, which are less prone to recall and selection biases. Despite these challenges a substantial literature on childhood cancer etiology has emerged but few strong environmental risk factors have been identified. Genetic studies are thus now coming to the fore with some success. The ultimate aim of epidemiologic studies is to reduce the population burden of childhood cancer by suggesting preventive measures or possibly by enabling early detection. Pediatr Blood Cancer 2013; 60: 1059-1062. © 2012 Wiley Periodicals, Inc.

Cohort Profile: The International Childhood Cancer Cohort Consortium (I4C)

Globally, a number of large infant/child prospective studies have been launched to examine environmental and genetic determinants of common diseases of children, such as asthma, developmental delay and behaviour abnormalities, as well as the consequences of early exposure for adult diseases. While several of these studies are relatively very large—over 100 000 subjects—and are adequately powered to examine their principal outcomes of interest, none of the individual studies are of sufficient size to examine the relationship between exposures they are measuring and rare diseases such as childhood cancer. To date, the few established risk factors for specific forms of childhood cancer have largely been identified in case-control studies. Yet, despite many such investigations evaluating postulated risk factors for paediatric malignancies during the past five decades, few consistently established aetiologic factors are known. Recent review papers have summarized many promising hypotheses, including pre-natal and post-natal exposure to pesticides, maternal and early infancy dietary factors, paternal pre-conception occupational exposures and smoking, the interplay of maternal or early postnatal immune system handling of common infections, determinants of high birth weight and other factors. Employment of prospective cohort follow-up of children and adolescents from pregnancy or birth using cohort or nested case-cohort designs, in conjunction with prospective biological sample collection, offers promising opportunities for advancing knowledge of aetiology. This is a result of improved assessment of parental and early life exposures, measurement of biological samples for pre-diagnostic effects, clarification of the temporal relationship between exposure and outcome, reduction of differential recall between parents of cases vs controls and the prospect of understanding the determinants of selection bias. The concept of bringing the various cohorts of infants and children together in an international collaboration arose during planning for the National Children’s Study (NCS), a childhood cohort study in the United States of 100 000 participants. Participants at a 2004 workshop convened to consider whether this cohort would be of sufficient size to include cancer as a feasible outcome; they concluded that this study would have insufficient power for this purpose due to the rarity of all forms of childhood cancer. However, a collaboration of the existing and planned large childhood cohorts globally might provide the power necessary to obtain prospective evidence on potential causes of childhood cancer. This idea was developed further and a proposal was presented to the National Institute for Child Health and Human Development (NICHD), National Cancer Institute (NCI) and the US Environmental Protection Agency (EPA). Along with funding support from the National Institute of Health’s Office of Rare Diseases, these organizations held a workshop in 2005, bringing together representatives from 11 cohorts in four continents, accounting for 700 000 children (Table 1), as well as experts in epidemiology, paediatric oncology, genetics, toxicology and other disciplines. Its purpose * Corresponding author. U.S. Environmental Protection Agency, National Center for Environmental Assessment, 1200 Pennsylvania Avenue, NW, 8623D, Washington, DC, 20460 USA. E-mail: brown.rebecca@epa.gov 1 National Center for Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Washington, DC, USA. 2 Murdoch Childrens Research Institute, Melbourne, Australia. 3 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. 4 National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. 5 National Center for Maternal and Infant Health, Peking University Health Science Center, Beijing, China. 6 Department of Epidemiology, University of California, Los Angeles, CA, USA. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org Published by Oxford University Press on behalf of the International Epidemiological Association The Author 2007; all rights reserved. Advance Access publication 25 January 2007 International Journal of Epidemiology 2007;36:724–730 doi:10.1093/ije/dyl299