A population-based linkage of administrative data sources to investigate associations between assisted reproductive technology and cancer risk in Great Britain

Introduction: Exposure of women to supra-physiological hormone levels and exposure of early embryos to artificial environments could increase cancer risks in women who have had assisted reproductive technology (ART) and children born after ART. This study aims to investigate possible associations by linking routinely collected data. Methods: Records of 255,786 ART treated women and 106, 013 ART conceived children in Great Britain (1991-2010) were linked to national registries of England & Wales and of Scotland, and the National Register of Childhood Tumours to obtain cancer outcome status. Observed cancers were compared against age and sex specific expectation, based on national rates. Analyses were stratified for potential moderating, mediating and confounding factors; 95% confidence-intervals, 2-sided P-values and trends were calculated assuming a Poisson distribution. Results: In 2,257,789 person-years of observation in ART treated women with an average follow-up of 8.8 years, no increased risk of corpus uteri (SIR-1.12; 95%CI 0.95-1.30), or invasive breast (SIR-0.96; 0.2-1.00) cancer was detected. An increased risk of ovarian cancer (SIR-1·39; 1·26-1·53), both invasive (SIR-1·40; 1·24-1·58) and borderline (SIR-1·36; 1·15-1·60) was limited to women with endometriosis, nulliparity, or both. There was no increased risk of ovarian tumours in women treated for only male factor or unexplained infertility. In 700,705 person-years of observation in ART conceived children with an average follow-up of 6.6 years, no overall increased risk of childhood cancer was found (SIR-0.98; 0.81-1.19). An excess of hepatoblastoma (SIR-3.64; 1.34-7.93), was likely mediated by low-birthweight (Birthweight<2500g SIR-10.29; 3.34-24.02). Conclusion: Routinely collected national data, linked to investigate cancer outcomes after ART, were largely reassuring, although some specific increases were detected. There was no convincing evidence relating increased risks to ART procedures per se. Average follow-up was 8.8 years for women and 6.6 years for children, therefore longer follow-up is required to confirm impact on lifetime risks

International benchmarking of childhood cancer survival by stage at diagnosis: The BENCHISTA project protocol

BACKGROUND: Several studies have shown significant variation in overall survival rates from childhood cancer between countries, using population-based cancer registry (PBCR) data for all cancers combined and for many individual tumour types among children. Without accurate and comparable data on Tumour stage at diagnosis, it is difficult to define the reasons for these survival differences. This is because measurement systems designed for adult cancers do not apply to children's cancers and cancer registries often hold limited information on paediatric tumour stage and the data sources used to define it. AIMS: The BENCHISTA project aims to test the application of the international consensus "Toronto Staging Guidelines" (TG) for paediatric tumours by European and non-European PBCRs for six common paediatric solid tumours so that reliable comparisons of stage at diagnosis and survival rates by stage can be made to understand any differences. A secondary aim is to test the data availability and completeness of collection of several 'Toronto' consensus non-stage prognostic factors, treatment types given, occurrence of relapse/progression and cause of death as a descriptive feasibility study. METHODS: PBCRs will use their permitted data access channels to apply the Toronto staging guidelines to all incident cases of six solid childhood cancers (medulloblastoma, osteosarcoma, Ewings sarcoma, rhabdomyosarcoma, neuroblastoma and Wilms tumour) diagnosed in a consecutive three-year period within 2014-2017 in their population. Each registry will provide a de-identified patient-level dataset including tumour stage at diagnosis, with only the contributing registry holding the information that would be needed to re-identify the patients. Where available to the registry, patient-level data on 'Toronto' non-stage prognostic factors, treatments given and clinical outcomes (relapse/progression/cause of death) will be included. More than 60 PBCRs have been involved in defining the patient-level dataset items and intend to participate by contributing their population-level data. Tumour-specific on-line training workshops with clinical experts are available to cancer registry staff to assist them in applying the Toronto staging guidelines in a consistent manner. There is also a project-specific help desk for discussion of difficult cases and promotion of the CanStaging online tools, developed through the International Association of Cancer Registries, to further ensure standardisation of data collection. Country-specific stage distribution and observed survival by stage at diagnosis will be calculated for each tumour type to compare survival between countries or large geographical regions. DISCUSSION: This study will be promote and enhance the collection of standardized staging data for childhood cancer by European and non-European population-based cancer registries. Therefore, this project can be seen as a feasibility project of widespread use of Toronto Staging at a population-level by cancer registries, specifying the data sources used and testing how well standardized the processes can be. Variation in tumour stage distribution could be due to real differences, to different diagnostic practices between countries and/or to variability in how cancer registries assign Toronto stage. This work also aims to strengthen working relationships between cancer registries, clinical services and cancer-specific clinical study groups, which is important for improving patient outcomes and stimulating research

Investigating long-term outcomes and cure for children and young people diagnosed with cancer

Survival for children and young adults (CYA) diagnosed with cancer has improved substantially over recent decades, with over 80% currently diagnosed expected to survive at least 5-years. However, survivors are at increased risk of the late effects of their treatment, with many reporting chronic health conditions in later life. The purpose of this project was to investigate cure and long-term health outcomes in CYA with cancer in Yorkshire using data from a population-based cancer registry. The study included 5471 patients diagnosed with a primary tumour in Yorkshire between 1990 and 2011 aged under 30. Statistical cure models were utilised to describe survival trends. These models simultaneously estimate the percentage ‘cured’ and the survival of those ‘uncured’. The percentage cured is a summary of long-term survival while the median survival time of the uncured provides important information on those who are not long-term survivors. Generally for most diagnostic groups there was an improvement in survival over time which was mainly driven by an increase in the proportion of patients cured rather than an increase in the survival of the uncured. Long-term morbidity was assessed via linkage to hospital admission data for respiratory and cardiovascular disease and subsequent tumours obtained from cancer registrations. Long-term CYA had increased risk of each of these outcomes compared to the general population. Analysis incorporating the cumulative burden of all subsequent neoplasms and all respiratory and cardiovascular hospitalisations combined found that by age 40, an individual experienced an average of 2 of these events, mainly driven by hospitalisations for respiratory conditions. Findings from this study provide an evidence base to aid risk-stratification for the long-term follow-up care for this high risk population

Risks of adverse health and social outcomes among childhood cancer survivors

As a result of improvement in survival after childhood cancer, there are now increasing numbers of long-term survivors of childhood cancer living in the United Kingdom and across Europe. Specific groups of these childhood cancer survivors experience substantial excess risks of adverse health and social outcomes. Using the population-based British Childhood Cancer Survivor Study (BCCSS) the following areas were investigated: (I) The proportion of survivors on regular long-term hospital follow-up using risk stratification levels of care developed by the BCCSS in partnership with the National Cancer Survivorship Initiative. (2) The risks of adverse health and social outcomes using record-linkage and a self-reported questionnaire to assess which survivors of central nervous system tumours were at excess risk compared to the general population. (3) The risk of hospitalisation due to cerebrovascular conditions among childhood cancer survivors by electronic record linkage with Hospital Episode Statistics. Using the European PanCareSurFup cohort, the excess risks of genitourinary subsequent primary neoplasms were investigated among five-year survivors of childhood cancer. This thesis quantifies the risks experienced by childhood cancer survivors in four areas and provides an evidence-base for risk stratification by healthcare professionals caring for survivors

Childhood cancer and magnetic fields from high-voltage power lines in England and Wales: a case–control study

BACKGROUND: Epidemiological evidence suggests that chronic low-intensity extremely-low-frequency magnetic-field exposure is associated with increased risk of childhood leukaemia; it is not certain the association is causal. METHODS: We report a national case-control study relating childhood cancer risk to the average magnetic field from high-voltage overhead power lines at the child's home address at birth during the year of birth, estimated using National Grid records. From the National Registry of Childhood Tumours, we obtained records of 28,968 children born in England and Wales during 1962-1995 and diagnosed in Britain under age 15. We selected controls from birth registers, matching individually by sex, period of birth, and birth registration district. No participation by cases or controls was required. RESULTS: The estimated relative risk for each 0.2 μT increase in magnetic field was 1.14 (95% confidence interval 0.57 to 2.32) for leukaemia, 0.80 (0.43-1.51) for CNS/brain tumours, and 1.34 (0.84-2.15) for other cancers. CONCLUSION: Although not statistically significant, the estimate for childhood leukaemia resembles results of comparable studies. Assuming causality, the estimated attributable risk is below one case per year. Magnetic-field exposure during the year of birth is unlikely to be the whole cause of the association with distance from overhead power lines that we previously reported

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case – control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers

Extremely Low Frequency Electromagnetic Field (ELF-EMF) and childhood leukemia near transmission lines: a review

This article presents a systematic review of most cited studies from developed countries those shed light on the potential relation between childhood leukemia and extremely low frequency electromagnetic field (ELF-EMF). All the findings of articles critically segregated as per some neglected parameters like number of samples, exposure duration, frequency range, distance from the radiation sources, and location during measurement of magnetic field density near power lines. Literature of major 50 studies are divided according to pooled analysis / meta-analysis, residential zone assessment and case-control studies

The state of research into children with cancer across Europe : new policies for a new decade

Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.peer-reviewe

Cancer risk in children born after donor ART

STUDY QUESTION: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population? SUMMARY ANSWER: This study showed no overall increased risk of childhood cancer in individuals born after donor ART. WHAT IS KNOWN ALREADY: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992–2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992–2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles. MAIN RESULTS AND THE ROLE OF CHANCE In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43–1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25–37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight. LIMITATIONS REASONS FOR CAUTION Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests