Changing geographical patterns and trends in cancer incidence in children and adolescents in Europe, 1991-2010 (Automated Childhood Cancer Information System): a population-based study.

BACKGROUND: A deceleration in the increase in cancer incidence in children and adolescents has been reported in several national and regional studies in Europe. Based on a large database representing 1·3 billion person-years over the period 1991-2010, we provide a consolidated report on cancer incidence trends at ages 0-19 years. METHODS: We invited all population-based cancer registries operating in European countries to participate in this population-based registry study. We requested a listing of individual records of cancer cases, including sex, age, date of birth, date of cancer diagnosis, tumour sequence number, primary site, morphology, behaviour, and the most valid basis of diagnosis. We also requested population counts in each calendar year by sex and age for the registration area, from official national sources, and specific information about the covered area and registration practices. An eligible registry could become a contributor if it provided quality data for all complete calendar years in the period 1991-2010. Incidence rates and the average annual percentage change with 95% CIs were reported for all cancers and major diagnostic groups, by region and overall, separately for children (age 0-14 years) and adolescents (age 15-19 years). We examined and quantified the stability of the trends with joinpoint analyses. FINDINGS: For the years 1991-2010, 53 registries in 19 countries contributed a total of 180 335 unique cases. We excluded 15 162 (8·4%) of 180 335 cases due to differing practices of registration, and considered the quality indicators for the 165 173 cases included to be satisfactory. The average annual age-standardised incidence was 137·5 (95% CI 136·7-138·3) per million person-years and incidence increased significantly by 0·54% (0·44-0·65) per year in children (age 0-14 years) with no change in trend. In adolescents, the combined European incidence was 176·2 (174·4-178·0) per million person-years based on all 35 138 eligible cases and increased significantly by 0·96% (0·73-1·19) per year, although recent changes in rates among adolescents suggest a deceleration in this increasing trend. We observed temporal variations in trends by age group, geographical region, and diagnostic group. The combined age-standardised incidence of leukaemia based on 48 458 cases in children was 46·9 (46·5-47·3) per million person-years and increased significantly by 0·66% (0·48-0·84) per year. The average overall incidence of leukaemia in adolescents was 23·6 (22·9-24·3) per million person-years, based on 4702 cases, and the average annual change was 0·93% (0·49-1·37). We also observed increasing incidence of lymphoma in adolescents (average annual change 1·04% [0·65-1·44], malignant CNS tumours in children (average annual change 0·49% [0·20-0·77]), and other tumours in both children (average annual change 0·56 [0·40-0·72]) and adolescents (average annual change 1·17 [0·82-1·53]). INTERPRETATION: Improvements in the diagnosis and registration of cancers over time could partly explain the observed increase in incidence, although some changes in underlying putative risk factors cannot be excluded. Cancer incidence trends in this young population require continued monitoring at an international level. FUNDING: Federal Ministry of Health of the Federal German Government, the European Union's Seventh Framework Programme, and International Agency for Research on Cancer.

Childhood cancer survival in Europe 1999-2007: results of EUROCARE-5--a population-based study.

BACKGROUND: Survival and cure rates for childhood cancers in Europe have greatly improved over the past 40 years and are mostly good, although not in all European countries. The EUROCARE-5 survival study estimates survival of children diagnosed with cancer between 2000 and 2007, assesses whether survival differences among European countries have changed, and investigates changes from 1999 to 2007. METHODS: We analysed survival data for 157,499 children (age 0-14 years) diagnosed between Jan 1, 1978 and Dec 31, 2007. They came from 74 population-based cancer registries in 29 countries. We calculated observed, country-weighted 1-year, 3-year, and 5-year survival for major cancers and all cancers combined. For comparison between countries, we used the corrected group prognosis method to provide survival probabilities adjusted for multiple confounders (sex, age, period of diagnosis, and, for all cancers combined without CNS cancers, casemix). Age-adjusted survival differences by area and calendar period were calculated with period analysis and were given for all cancers combined and the major cancers. FINDINGS: We analysed 59,579 cases. For all cancers combined for children diagnosed in 2000-07, 1-year survival was 90.6% (95% CI 90.2-90.9), 3-year survival was 81.0 % (95% CI 80.5-81.4), and 5-year survival was 77.9% (95% CI 77.4-78.3). For all cancers combined, 5-year survival rose from 76.1% (74.4-77.7) for 1999-2001, to 79.1% (77.3-80.7) for 2005-07 (hazard ratio 0.973, 95% CI 0.965-0.982, p<0.0001). The greatest improvements were in eastern Europe, where 5-year survival rose from 65.2% (95% CI 63.1-67.3) in 1999-2001, to 70.2% (67.9-72.3) in 2005-07. Europe-wide average yearly change in mortality (hazard ratio) was 0.939 (95% CI 0.919-0.960) for acute lymphoid leukaemia, 0.959 (0.933-0.986) for acute myeloid leukaemia, and 0.940 (0.897-0.984) for non-Hodgkin lymphoma. Mortality for all of Europe did not change significantly for Hodgkin's lymphoma, Burkitt's lymphoma, CNS tumours, neuroblastoma, Wilms' tumour, Ewing's sarcoma, osteosarcoma, and rhabdomyosarcoma. Disparities for 5-year survival persisted between countries and regions, ranging from 70% to 82% (for 2005-07). INTERPRETATION: Several reasons might explain persisting inequalities. The lack of health-care resources is probably most important, especially in some eastern European countries with limited drug supply, lack of specialised centres with multidisciplinary teams, delayed diagnosis and treatment, poor management of treatment, and drug toxicity. In the short term, cross-border care and collaborative programmes could help to narrow the survival gaps in Europe. FUNDING: Italian Ministry of Health, European Commission, Compagnia di San Paolo Foundation.

Survival and cure trends for European children, adolescents and young adults diagnosed with acute lymphoblastic leukemia from 1982 to 2002.

Proportion cured is a potentially more informative cancer outcome measurement than 5-year survival. We present population-based estimates of cure for young patients diagnosed with acute lymphoblastic leukemia in Europe from 1982 to 2002. Thirty-five European cancer registries provided data. Survival was estimated by age, period of diagnosis and European region, and used as input for parametric cure models, which assume cured patients have the same mortality as the general population. For acute lymphoblastic leukemia diagnosed in 1-14 year olds in 2000-2002, over 77% were estimated cured. The proportion cured improved significantly over the study period: an impressive 26-58% in infants (up to 1 year), 70-90% in 1-4 year olds, 63-86% in 5-9 year olds, 52-77% in 10-14 year olds, and 44-50% in 15-24 year olds. Regional variations in proportion cured reduced over time for 1-14 year-olds, but persisted in infants and 15-24 year olds. Five-year survival was always slightly higher than proportion cured. Considerable proportions of young patients were estimated cured of acute lymphoblastic leukemia. Nevertheless, a small excess risk of death persisted beyond five years after diagnosis when patients remained at risk for late treatment effects, late relapses and second primaries.

A very rare cancer in Down syndrome: medulloblastoma. Epidemiological data from 13 countries.

Persons with Down syndrome (DS) uniquely have an increased frequency of leukemias but a decreased total frequency of solid tumors. The distribution and frequency of specific types of brain tumors have never been studied in DS. We evaluated the frequency of primary neural cell embryonal tumors and gliomas in a large international data set. The observed number of children with DS having a medulloblastoma, central nervous system primitive neuroectodermal tumor (CNS-PNET) or glial tumor was compared to the expected number. Data were collected from cancer registries or brain tumor registries in 13 countries of Europe, America, Asia and Oceania. The number of DS children with each category of tumor was treated as a Poisson variable with mean equal to 0.000884 times the total number of registrations in that category. Among 8,043 neural cell embryonal tumors (6,882 medulloblastomas and 1,161 CNS-PNETs), only one patient with medulloblastoma had DS, while 7.11 children in total and 6.08 with medulloblastoma were expected to have DS. (p 0.016 and 0.0066 respectively). Among 13,797 children with glioma, 10 had DS, whereas 12.2 were expected. Children with DS appear to be specifically protected against primary neural cell embryonal tumors of the CNS, whereas gliomas occur at the same frequency as in the general population. A similar protection against neuroblastoma, the principal extracranial neural cell embryonal tumor, has been observed in children with DS. Additional genetic material on the supernumerary chromosome 21 may protect against embryonal neural cell tumor development.

Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

BACKGROUND: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? METHODS: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. RESULTS: ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CONCLUSIONS: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Neuroblastoma in Spain: Linking the national clinical database and epidemiological registries - A study by the Joint Action on Rare Cancers.

PURPOSE: Linkage between clinical databases and population-based cancer registries may serve to evaluate European Reference Networks' (ERNs) activity, by monitoring the proportion of patients benefiting from these and their impact on survival at a population level. To test this, a study targeting neuroblastoma (Nb) was conducted in Spain by the European Joint Action on Rare Cancers. MATERIAL AND METHODS: Subjects: Nb cases, incident 1999-2017, aged < 15 years. Linkage included: Spanish Neuroblastoma Clinical Database (NbCDB) (1217 cases); Spanish Registry of Childhood Tumours (RETI) (1514 cases); and 10 regional population-based registries (RPBCRs) which cover 33% of the childhood population (332 cases). Linkage was semiautomatic. We estimated completeness, incidence, contribution, deficit, and 5-year survival in the databases and specific subsets. RESULTS: National completeness estimates for RETI and NbCDB were 91% and 72% respectively, using the Spanish RPBCRs on International Incidence of Childhood Cancer (https://iicc.iarc.fr/) as reference. RPBCRs' specific contribution was 1.6%. Linkage required manual crossover in 54% of the semiautomatic matches. Five-year survival was 74% (0-14 years) and 90% (0-18 months). CONCLUSIONS: All three databases were incomplete as regards Spain as a whole and should therefore be combined to achieve full childhood cancer registration. A unique personal patient identifier could facilitate such linkage. Most children have access to Nb clinical trials. Consolidated interconnections between the national registry and clinical registries (including ERNs and paediatric oncology clinical groups) should be established to evaluate outcomes.

The histology of brain tumors for 67 331 children and 671 085 adults diagnosed in 60 countries during 2000-2014: a global, population-based study (CONCORD-3).

BACKGROUND: Global variations in survival for brain tumors are very wide when all histological types are considered together. Appraisal of international differences should be informed by the distribution of histology, but little is known beyond Europe and North America. METHODS: The source for the analysis was the CONCORD database, a program of global surveillance of cancer survival trends, which includes the tumor records of individual patients from more than 300 population-based cancer registries. We considered all patients aged 0-99 years who were diagnosed with a primary brain tumor during 2000-2014, whether malignant or nonmalignant. We presented the histology distribution of these tumors, for patients diagnosed during 2000-2004, 2005-2009, and 2010-2014. RESULTS: Records were submitted from 60 countries on 5 continents, 67 331 for children and 671 085 for adults. After exclusion of irrelevant morphology codes, the final study population comprised 60 783 children and 602 112 adults. Only 59 of 60 countries covered in CONCORD-3 were included because none of the Mexican records were eligible. We defined 12 histology groups for children, and 11 for adults. In children (0-14 years), the proportion of low-grade astrocytomas ranged between 6% and 50%. Medulloblastoma was the most common subtype in countries where low-grade astrocytoma was less commonly reported. In adults (15-99 years), the proportion of glioblastomas varied between 9% and 69%. International comparisons were made difficult by wide differences in the proportion of tumors with unspecified histology, which accounted for up to 52% of diagnoses in children and up to 65% in adults. CONCLUSIONS: To our knowledge, this is the first account of the global histology distribution of brain tumors, in children and adults. Our findings provide insights into the practices and the quality of cancer registration worldwide.

Worldwide comparison of survival from childhood leukaemia for 1995-2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries.

BACKGROUND: Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. METHODS: Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (<1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). FINDINGS: We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year age-standardised net survival for all lymphoid leukaemias combined ranged from 10·6% (95% CI 3·1-18·2) in the Chinese registries to 86·8% (81·6-92·0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52·4% (95% CI 42·8-61·9) in Cali, Colombia, to 91·6% (89·5-93·6) in the German registries, and for AML ranged from 33·3% (18·9-47·7) in Bulgaria to 78·2% (72·0-84·3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. INTERPRETATION: Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood cancer survival. FUNDING: Canadian Partnership Against Cancer, Cancer Focus Northern Ireland, Cancer Institute New South Wales, Cancer Research UK, US Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, and the University of Kentucky.

Childhood central nervous system tumours--incidence and survival in Europe (1978-1997): report from Automated Childhood Cancer Information System project.

This paper describes the incidence and survival of childhood central nervous system (CNS) tumours in Europe for the period 1978-1997. A total of 19,531 cases, aged 0-14 years, from the ACCIS database were analysed by five regions: the British Isles, East, North, South, and West. Overall age-standardised incidence rate (ASR) of CNS tumours in Europe (1988-1997) was 29.9 per million, with the highest rates in the North. Astrocytoma (ASR=11.8), primitive neuroectodermal tumours (PNET) (ASR=6.5) and ependymoma (ASR=3.4) were the most frequent types. Incidence increased significantly during 1978-1997, on average by 1.7% per year. Diagnostic methods may partially explain incidence rates and trends, although a role of variations in risk factors cannot be excluded. Overall 5-year survival was 64% and varied between 72% in the North and 53% in the East. PNET had the poorest prognosis (49%) and astrocytoma the best (75%). Survival has improved by 29% since late 1970s. The positive trends were seen in all regions, although the interregional differences persisted, as a reflection of the different healthcare systems.

Childhood soft tissue sarcomas incidence and survival in European children (1978-1997): report from the Automated Childhood Cancer Information System project.

This population-based study is based on 5802 cases of soft tissue sarcomas (STS) in children aged 0-14 years extracted from the database of the Automated Childhood Cancer Information System (ACCIS) and registered in population-based cancer registries in Europe for the period 1978-1997. STS represent almost 8% of neoplasms in children, almost half of whom are less than 5 years at diagnosis. Rhabdomyosarcoma is the most frequent childhood STS (50%). During 1988-1997 the age-standardised incidence of STS in Europe was 9.1 per million children, lowest in the West and East and highest in the North. The incidence of STS increased almost 2% per year over the period 1978-1997, attributable mostly to increase in genito-urinary rhabdomyosarcoma. Prognosis of children with STS was related to age and site of tumour. Five-year survival of children with STS increased from 46% in 1978-1977 to 66% in 1993-1997, reaching 74% in the North for those diagnosed in 1993-1997. This improvement is ascribed to therapy advances.

Incidence Patterns and Trends of non-Central Nervous System Solid Tumours in Children and Adolescents. A Collaborative Study of the Spanish Population Based Cancer Registries.

OBJECTIVE: To describe incidence patterns and trends in children (0-14 years) and adolescents (15-19 age-range) with solid tumours, except those of central nervous system (CNS), in Spain. METHODS: Cases were drawn from eleven Spanish population-based cancer registries. Incidence was estimated for the period 1983-2007 and trends were evaluated using Joinpoint regression analysis. RESULTS: The studied tumour groups accounted for 36% of total childhood cancers and 47.6% of those diagnosed in adolescence with annual rates per million of 53.5 and 89.3 respectively. In children 0 to 14 years of age, Neuroblastoma (NB) was the commonest (7.8%) followed by Soft-tissue sarcomas (STS) (6.3%), bone tumours (BT) (6.2%) and renal tumours (RT) (4.5%). NB was the most frequently diagnosed tumour before the 5th birthday, while STS and BT were the commonest at 5-9 years of age, and BT and Carcinoma and other epithelial tumours (COET) at 10-14. COET presented the highest incidence in adolescents, followed by germ-cell tumours (GCT), BT and STS. These four diagnostic groups accounted for 94% of total non-CNS solid tumours, in adolescents. Overall incidence rates increased significantly in children up to 1996 with an annual percentage change (APC) of 2.6% (95%CI: 1.7; 3.6). NB and COET showed significant time trend (APCs: 1.4% and 3.8% respectively) while other tumour groups such as RT, STS, BT or GCT had no significant changes over time. A significant increase was present in NB under the age of 5 and in BT and STS in children aged 10-14 years. In adolescents there were significant increases for all tumours combined (APC=2.7; 95%CI: 1.8-3.6) and for STS, GCT and COET (APCs: 3.2%, 4.4% and 3.5% respectively), while other tumour groups such as hepatic tumours, BT or thyroid carcinomas showed a decreasing trend or no increase. CONCLUSIONS: Overall, the incidence of the studied cancers in children increased along the period 1983-1996 with no posterior significant rise, while the incidence in adolescents increased significantly over the whole period 1983-2007. Several specific tumour groups showed significant rises or decrements in childhood or adolescence, although the small number of cases precludes showing significant trends or inflexion points.

Registration of childhood cancer: Moving towards pan-European coverage?

Cancer is relatively rare in childhood, but it contributes considerably to childhood mortality, years of life lost per person and late effects in survivors. Large populations need to be covered to set up meaningful studies of these rare conditions. Cancer registries ensure cancer surveillance, thus providing the basis for research as well as policy decisions. In this paper we examine coverage of childhood population by cancer registries in Europe and encourage national cancer registration. Over 200 cancer registries in various stages of development were identified as collecting data on childhood cancer patients in Europe. They cover 52% of the childhood population in the World Health Organisation (WHO) European region and 83% in the European Union (EU). More than 80% of this coverage is ensured by nationwide data collection, which is ongoing in 29 European countries. Overall coverage of the childhood population could increase to around 98%, if the recently established cancer registries start producing results and others improve their quality and dissemination plans. Paediatric cancer registries are being established with increasing frequency even in the areas covered by general cancer registries, and they tend to be national. Compared with regional registration, national cancer registries are more cost-effective, record larger number of cases, they can achieve higher completeness, less biased incidence and survival estimates and they are conditioned for national and international research. National registration of childhood cancer should be the rule in Europe, so that accurate regional, nation-wide and international statistics can provide solid baselines for research, clinical practice and public health policy. Governmental support and stakeholders' involvement are indispensable to guarantee optimal data quality and completeness.

Population-based incidence of childhood leukaemias and lymphomas in Spain (1993-2002).

The aim of this study was to estimate the incidence of leukaemias and lymphomas in children according to the International Classification of Childhood Cancer third edition (ICCC-3) in the population covered by the Girona, Valencia, and Zaragoza population-based cancer registries and compare it with the incidence rates in other European countries. All haematological malignancies (HMs) registered between 1993 and 2002 in children below 15 years of age were included in the study. Pathological and haematological diagnoses were reviewed, recoded according to International Classification of Diseases for Oncology-3 and reclassified on the basis of ICCC-3. Sex and age-adjusted incidence rates were calculated, using the world population as standard. Five hundred and seventy-one HMs were registered in the Girona, Valencia and Zaragoza Cancer Registries during the study period. According to ICCC-3, precursor cell leukaemias were the most frequent HMs in children and constituted 60% of all HMs (an age-adjusted incidence rate of 42.7 per million children-years). The second most frequent childhood HM was Hodgkin lymphoma (11.2% of all HMs), yielding an age-adjusted standardized incidence rate of 6.3 per million children-years. With regard to myeloid lineage, acute myeloid leukaemias were the most frequent with a rate of 7.9 per million children-years. The standardized incidence rates for lymphoid leukaemia (1.19) and Burkitt lymphoma (3.94) were statistically higher than the rates observed in Europe. Compared with European data, Spain has a high incidence of lymphoid leukaemias and lymphomas. In particular, a high incidence of Burkitt lymphoma was observed. The causes of this geographical variation are still unknown.

Survival of European children and young adults with cancer diagnosed 1995-2002.

This study analyses survival in 40,392 children (age 0-14 years) and 30,187 adolescents/young adults (age 15-24 years) diagnosed with cancer between 1995 and 2002. The cases were from 83 European population-based cancer registries in 23 countries participating in EUROCARE-4. Five-year survival in countries and in regional groupings of countries was compared for all cancers combined and for major cancers. Survival for 15 rare cancers in children was also analysed. Five-year survival for all cancers combined was 81% in children and 87% in adolescents/young adults. Between-country survival differences narrowed for both children and adolescents/young adults. Relative risk of death reduced significantly, by 8% in children and by 13% in adolescents/young adults, from 1995-1999 to 2000-2002. Survival improved significantly over time for acute lymphoid leukaemia and primitive neuroectodermal tumours in children and for non-Hodgkin lymphoma in adolescents/young adults. Cancer survival in patients <25 years is poorly documented in Eastern European countries. Complete cancer registration should be a priority for these countries as an essential part of a policy for effective cancer control in Europe.

Family cancer history and risk of brain tumors in children: results of the SEARCH international brain tumor study.

OBJECTIVE: To examine whether childhood brain tumors (CBTs) are associated with a family history of brain tumors or other cancers in an international case-control study. METHODS: Cancers in children's first- and second-degree relatives were ascertained by interview with parents of 620 children with astroglial tumors, 255 with primitive neuroectodermal tumors, 324 with other CBTs, and 2,218 controls from Australia, Canada, France, Israel, Italy, Spain, and the US. These were used with histories of neurofibromatosis or tuberous sclerosis to exclude in subanalyses children with Li-Fraumeni or other hereditary syndromes predisposing to brain tumors. RESULTS: A first- or second-degree relative of 4% of children with astroglial tumors, 6% with PNET, 5% with other CBTs, and 5% of controls had had a brain tumor. Any potential differences were statistically non-significant, including when focusing on relatives diagnosed in childhood. In the US, where anatomical sites of relatives' other cancers were known, CBT occurrence was not associated with any other specific site. Results were not markedly altered by exclusion of children with hereditary syndromes. CONCLUSION: Consistent with most prior studies using these methods, we observed no strong relationship between CBT occurrence and cancers in family members.

Farm-related exposures and childhood brain tumours in seven countries: results from the SEARCH International Brain Tumour Study.

A total of 1218 cases of childhood brain tumours (CBT) and 2223 control subjects from the general population were included in a population-based case-control study conducted in nine centres in seven countries. Mothers were asked about farm- or agriculture-related exposures. Significantly elevated odds ratios (OR) for CBT were associated with children's personal and maternal prenatal exposure while living on a farm with pigs (child OR = 1.7, mother OR = 2.3), horses (child OR = 1.6, mother OR = 1.8), dogs (child OR = 1.5, mother OR = 1.5) and cats (child OR = 1.5, mother OR = 1.7). Children who were exposed to pigs, horses and cats combined, while living on a farm, had a threefold elevated OR for CBT. Increased ORs for primitive neuroectodermal tumours (PNET) were associated with children's farm exposure to dogs (OR = 1.9) and cats (OR = 2.2), and maternal farm exposure to pigs (OR = 4.2). The OR for CBT was elevated (OR = 2.3) for children of mothers who had preconception/prenatal farm- or agriculture-related employment involving potential contact with animals, relative to no farm- or agriculture-related employment. In particular, increased ORs for CBT were observed for children of mothers who were employed as general farmers (OR = 4.1) or general farm workers (OR = 3.8). During the 5 years preceding the index child's birth, maternal exposures were related to CBT, relative to no maternal exposure to agricultural chemicals or animal products: fertilisers (OR = 1.8), pesticides (OR = 2.0), animal manure (OR = 2.0) and unprocessed wool (OR = 3.0). Our findings suggest that various farm-related exposures are positively associated with CBT and warrant further investigation into the public health importance of these associations.