RESUMO
PURPOSE: The United Kingdom Childhood Cancer Study's (UKCCS's) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age, comparing future healthcare patterns in 5-year cancer survivors to baseline activity seen in age- and sex-matched individuals from the general population. PARTICIPANTS: Predicated on a national childhood cancer case-control study conducted in the early 1990s (4430 cases, 9753 controls) in England, Scotland and Wales, the case population comprises 3125 cancer survivors (>5 years), and the control population 7156 age- and sex-matched individuals from the general population who did not have cancer as a child. Participants are now being followed up via linkage to national administrative healthcare databases (deaths, cancers and secondary care hospital activity). FINDINGS TO DATE: Enabling the creation of cohorts with minimal selection bias and loss to follow-up, the original case-control study registered all newly diagnosed cases of childhood cancer and their corresponding controls, regardless of their family's participation. Early findings based on the registered case population found marked survival variations with age and sex across subtypes and differences with deprivation among acute lymphoblastic leukaemia (ALL) survivors. More recently, comparing the health-activity patterns of the case and control populations revealed that survivors of childhood ALL experienced excess outpatient and inpatient activity across their teenage/young adult years. Adding to increased risks of cancer and death and involving most clinical specialties, excesses were not related to routine follow-up monitoring and showed no signs of diminishing over time. FUTURE PLANS: With annual linkage updates, the UKCCS's maturing population-based matched cohorts provide the foundation for tracking the health of individuals through their lifetime. Comparing the experience of childhood cancer survivors to that of unaffected general-population counterparts, this will include examining subsequent morbidity and mortality, secondary care hospital activity and the impact of deprivation on longer term outcomes.
Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto Jovem , Humanos , Criança , Neoplasias/epidemiologia , Estudos de Casos e Controles , Fatores de Risco , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Studies examining the potential impact of mothers' health during pregnancy on the health of their offspring often rely on self-reported information gathered several years later. To assess the validity of this approach, we analysed data from a national case-control study of childhood cancer (diagnosed <15 years) that collected health information from both interviews and medical records. METHODS: Mothers' interview reports of infections and medications in pregnancy were compared with primary care records. Taking clinical diagnoses and prescriptions as the reference, sensitivity and specificity of maternal recall along with kappa coefficients of agreement were calculated. Differences in the odd ratios estimated using logistic regression for each information source were assessed using the proportional change in the odds ratio (OR). RESULTS: Mothers of 1624 cases and 2524 controls were interviewed â¼6 years (range 0-18 years) after their child's birth. Most drugs and infections were underreported; in general practitioner records, antibiotic prescriptions were nearly three times higher and infections >40% higher. Decreasing with increasing time since pregnancy, sensitivity was ⩽40% for most infections and all drugs except 'anti-epileptics and barbiturates' (sensitivity 80% among controls). ORs associated with individual drug/disease categories that were based on self-reported data varied from 26% lower to 26% higher than those based on medical records; reporting differences between mothers of cases and controls were not systematically in the same direction. CONCLUSIONS: The findings highlight the scale of under-reporting and poor validity of questionnaire-based studies conducted several years after pregnancy. Future research using prospectively collected data should be encouraged to minimize measurement errors.
Assuntos
Neoplasias , Gravidez , Feminino , Criança , Humanos , Autorrelato , Estudos de Casos e Controles , Neoplasias/epidemiologia , Prontuários Médicos , MãesRESUMO
OBJECTIVES: To examine morbidity and mortality among teenagers and young adults (TYAs) previously diagnosed with acute lymphoblastic leukaemia (ALL) in childhood, and compare to the general TYA population. DESIGN: National population-based sex-matched and age-matched case-control study converted into a matched cohort, with follow-up linkage to administrative healthcare databases. SETTING: The study population comprised all children (0-14 years) registered for primary care with the National Health Service (NHS) in England 1992-1996. PARTICIPANTS: 1082 5-year survivors of ALL diagnosed<15 years of age (1992-1996) and 2018 unaffected individuals; followed up to 15 March 2020. MAIN OUTCOME MEASURES: Associations with hospital activity, cancer and mortality were assessed using incidence rate ratios (IRR) and differences. RESULTS: Mortality in the 5-year ALL survivor cohort was 20 times higher than in the comparison cohort (rate ratio 21.3, 95% CI 11.2 to 45.6), and cancer incidence 10 times higher (IRR 9.9 95% CI 4.1 to 29.1). Hospital activity was increased for many clinical specialties, the strongest associations being for endocrinology; outpatient IRR 36.7, 95% CI 17.3 to 93.4 and inpatient 19.7, 95% CI 7.9 to 63.2 for males, and 11.0, 95% CI 6.2 to 21.1 and 6.2 95% CI 3.1 to 13.5, respectively, for females. Notable excesses were also evident for cardiology, neurology, ophthalmology, respiratory medicine and general medicine. Males were also more likely to attend gastroenterology; ear, nose and throat; urology; and dermatology, while females were more likely to be seen in plastic surgery and less likely in midwifery. CONCLUSIONS: Adding to excess risks of death and cancer, survivors of childhood ALL experience excess outpatient and inpatient activity across their TYA years, which is not related to routine follow-up monitoring. Involving most clinical specialties, associations are striking, showing no signs of diminishing over time. Recognising that all survivors are potentially at risk of late treatment-associated effects, our findings underscore the need to take prior ALL diagnosis into account when interpreting seemingly unrelated symptoms later in life.
Assuntos
Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Seguimentos , Humanos , Masculino , Morbidade , Neoplasias/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Fatores de Risco , Medicina Estatal , Sobreviventes , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Reports have suggested that children born by caesarean initiated before labour onset may be at increased risk of developing acute lymphoblastic leukaemia (ALL). However, with most data being derived from case-control study interviews, information on the underpinning reasons for caesarean section is sparse, and evidence is conflicting. OBJECTIVES: Use clinical records compiled at the time of delivery to investigate the association between childhood ALL and caesarean delivery; examining timing in relation to labour onset, and reasons for the procedure. METHODS: Data are from the UK Childhood Cancer Study, a population-based case-control study conducted in the 1990s, when caesarean section rates were relatively low, in England, Scotland, and Wales. Children with ALL were individually matched to two controls on sex, date of birth, and region of residence. Information on mode of delivery and complications was abstracted from obstetric records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models adjusted for matching variables and relevant covariates. RESULTS: Around 75% of the 1034 cases and 1914 controls were born through unassisted vaginal delivery. Caesarean delivery was as frequent in cases and controls (OR 1.07, 95% CI 0.84, 1.36). No association was observed between ALL and caesarean delivery either during or before labour, with adjusted ORs of 1.08 (95% CI 0.78, 1.48) and 1.09 (95% CI 0.78, 1.53), respectively. For B-cell ALL, the ORs were 1.14 (95% CI 0.81, 1.59) for caesarean during labour and 1.21 (95% CI 0.85, 1.72) for prelabour. The underpinning reasons for caesarean delivery differed between cases and controls; with preeclampsia, although very rare, being more common amongst cases born by caesarean (OR 8.91, 95% CI 1.48, 53.42). CONCLUSIONS: Our obstetric record-based study found no significant evidence that caesarean delivery increased the risk of childhood ALL, either overall or when carried out before labour.
Assuntos
Cesárea , Parto Obstétrico , Complicações do Trabalho de Parto/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Cesárea/métodos , Cesárea/estatística & dados numéricos , Criança , Correlação de Dados , Parto Obstétrico/métodos , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Sistemas de Informação/estatística & dados numéricos , Início do Trabalho de Parto , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Gravidez , Medição de Risco , Reino Unido/epidemiologiaRESUMO
Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.
Assuntos
Leucemia Mieloide Aguda/epidemiologia , Praguicidas/toxicidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Exposição Materna/efeitos adversos , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Risco , Fatores de RiscoRESUMO
The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Ordem de Nascimento , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Creches/estatística & dados numéricos , Pré-Escolar , Humanos , Infecções/epidemiologia , Infecções/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologiaRESUMO
PURPOSE: It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. METHODS: We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium. Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. RESULTS: Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukemia (ALL) was 0.93 [95% confidence interval (CI) 0.76, 1.14]. Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47), respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. CONCLUSIONS: Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed.
Assuntos
Exposição Materna/estatística & dados numéricos , Exposição Ocupacional/estatística & dados numéricos , Pintura/efeitos adversos , Exposição Paterna/estatística & dados numéricos , Leucemia-Linfoma Linfoblástico de Células Precursoras/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Exposição Materna/efeitos adversos , Exposição Ocupacional/efeitos adversos , Razão de Chances , Exposição Paterna/efeitos adversos , Gravidez , Fatores de RiscoRESUMO
Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.
Assuntos
Leucemia/etiologia , Exposição Materna/efeitos adversos , Exposição Ocupacional/efeitos adversos , Exposição Paterna/efeitos adversos , Praguicidas/efeitos adversos , Complicações Neoplásicas na Gravidez/etiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Agências Internacionais , Masculino , Metanálise como Assunto , Gravidez , Prognóstico , Fatores de RiscoRESUMO
Positive associations have been reported between the measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth-weight-for-gestational-age and proportion of optimal birth weight (POBW)-were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI: 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one-standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI: 0.77, 0.95), respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin-like growth factors. © 2013 UICC.
Assuntos
Desenvolvimento Fetal , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Peso ao Nascer , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Recém-Nascido , GravidezRESUMO
BACKGROUND: Heavy birthweight is one of the few established risk factors for childhood acute lymphoblastic leukaemia (ALL). To provide new insight into this relationship, particularly at the extremes (<1500 and > 4500 g), we pooled data from three of the largest childhood cancer case-control studies ever conducted. METHODS: Birthweight and gestational age on 4075 children with ALL and 12,065 controls were collected during the course of three studies conducted in the USA, the UK and Germany in the 1990s. Information was obtained from mothers at interview, and the impact of bias was evaluated using the UK study which accessed birth registrations of participants and non-participants. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. RESULTS: Children with ALL were, on average, heavier than controls at all gestations, the disparity being driven by a deficit of low-birthweight at all gestations and an excess of high-birthweight at ≥ 40 weeks. Overall, a 1.2 (95% CI 1.1-1.3) increase in ALL risk per kg increase in birthweight was observed; the ORs rising from 0.2 (0.1-0.7) at ≤ 1500 g through to 1.2 (0.9-1.6) at ≥ 4500 g; and 0.8 (0.7-0.9) <10th centile through to 1.3 (1.1-1.4) ≥ 90th centile. CONCLUSION: Our findings demonstrate the importance of looking across the full birthweight spectrum when examining associations with disease risk. The new observation of a deficit of very-low-birthweight cases at all gestations has aetiological and study design implications for future work examining not only the in utero origins of ALL, but also other childhood and adult cancers.
Assuntos
Peso ao Nascer , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Alemanha/epidemiologia , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Razão de Chances , Fatores de Risco , Reino Unido/epidemiologia , Estados Unidos/epidemiologiaRESUMO
Although there is increasing evidence that immune dysregulation in children who develop acute lymphoblastic leukemia (ALL) is detectable from birth, debate about the role of infectious exposures in infancy continues. With the aim of quantifying children's infectious exposures, investigators have used a number of infection exposure proxies, but there is a lack of consistency in findings, with some markers indicating increased ALL risks and others decreased risks, the disparity being evident both within and between studies. Accordingly, the authors conducted an in-depth analysis of key infection exposure proxies used in the United Kingdom Childhood Cancer Study, a national population-based case-control study conducted over the period 1991-1996, which combined data from medical records, parental interview, and population census. This longitudinal approach revealed the marked deterioration in immune response that emerged around 5 months prior to ALL diagnosis and confirmed that infectious diagnoses in the first year of life were significantly increased (P < 0.05) in children who developed leukemia between 2 and 14 years of age, as well as in those who had birth orders >1, were not breastfed, lived in deprived areas, or were diagnosed with eczema. By contrast, no association between infectious illness and preschool activity was detected, the lower infection levels among controls whose mothers reported attendance contributing to a significantly reduced ALL odds ratio.
Assuntos
Infecções/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Ordem de Nascimento , Aleitamento Materno , Estudos de Casos e Controles , Criança , Creches , Pré-Escolar , Eczema/complicações , Exposição Ambiental , Humanos , Lactente , Infecções/epidemiologia , Estudos Longitudinais , Razão de Chances , Áreas de Pobreza , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Análise de Regressão , Reino UnidoRESUMO
Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be possible through multi-center pooled analyses. Here, we review the rationale for identifying genetic risk variants for acute lymphoblastic leukemia and our proposed strategy for establishing the International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium.
Assuntos
Predisposição Genética para Doença , Cooperação Internacional , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Alelos , Criança , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Humanos , Polimorfismo Genético , Pesquisa/normas , Pesquisa/tendênciasRESUMO
OBJECTIVE: To examine childhood cancer risks associated with exposure to diagnostic radiation and ultrasound scans in utero and in early infancy (age 0-100 days). DESIGN: Case-control study. SETTING: England and Wales. PARTICIPANTS: 2690 childhood cancer cases and 4858 age, sex, and region matched controls from the United Kingdom Childhood Cancer Study (UKCCS), born 1976-96. MAIN OUTCOME MEASURES: Risk of all childhood cancer, leukaemia, lymphoma, and central nervous system tumours, measured by odds ratios. RESULTS: Logistic regression models conditioned on matching factors, with adjustment for maternal age and child's birth weight, showed no evidence of increased risk of childhood cancer with in utero exposure to ultrasound scans. Some indication existed of a slight increase in risk after in utero exposure to x rays for all cancers (odds ratio 1.l4, 95% confidence interval 0.90 to 1.45) and leukaemia (1.36, 0.91 to 2.02), but this was not statistically significant. Exposure to diagnostic x rays in early infancy (0-100 days) was associated with small, non-significant excess risks for all cancers and leukaemia, as well as increased risk of lymphoma (odds ratio 5.14, 1.27 to 20.78) on the basis of small numbers. CONCLUSIONS: Although the results for lymphoma need to be replicated, all of the findings indicate possible risks of cancer from radiation at doses lower than those associated with commonly used procedures such as computed tomography scans, suggesting the need for cautious use of diagnostic radiation imaging procedures to the abdomen/pelvis of the mother during pregnancy and in children at very young ages.
Assuntos
Neoplasias/epidemiologia , Diagnóstico Pré-Natal/efeitos adversos , Radiografia/efeitos adversos , Ultrassonografia/efeitos adversos , Estudos de Casos e Controles , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Humanos , Lactente , Masculino , Neoplasias/etiologia , Razão de Chances , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fatores de Risco , País de Gales/epidemiologiaRESUMO
BACKGROUND: Increased understanding of the relationship between lymphomas and co-morbidities is likely to provide valuable insights into the natural history of these disorders. METHODS: 761 cases with lymphoma (310 diffuse large B-cell [DLBCL]; 226 follicular [FL]; and 225 Hodgkin [HL]) and 761 unaffected age and sex matched controls were recruited and their histories of infection and non-infection diagnoses in primary care records were compared using negative binomial regression. RESULTS: No differences were observed between the infectious illness patterns of DLBCL and FL cases and their matched controls over the 15 years preceding lymphoma diagnosis. A marked excess of infectious illness episodes was recorded for HL cases compared to their controls; evident at least a decade prior to HL diagnosis. For non-infectious consultations an excess of case over control visits emerged 4-6 years before DLBCL and FL diagnosis; no specific co-morbidity associations were found. No case-control differences for non-infectious conditions were apparent for HL. CONCLUSION: There are substantial variations in patterns of illness prior to diagnosis of the three lymphoma subtypes examined. The excess of infectious diagnoses prior to HL may point to underlying immune abnormality, but there was no suggestion of this for DLBCL and FL where a generalized excess of non-infectious conditions was evident.
Assuntos
Linfoma/diagnóstico , Linfoma/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologiaRESUMO
Autoimmune disorders are more frequent in women, whereas most non-Hodgkin lymphomas (NHLs) are common in men; yet, sexspecific autoimmunelymphoma associations are rarely reported. Detailed data on autoimmune disease were abstracted from medical records of 791 cases (including 316 diffuse large B-cell lymphomas (DLBCLs); 228 follicular lymphomas (FLs); 127 marginal zone lymphomas (MZLs); 64 T-cell lymphomas and 38 mantle cell lymphomas) and 872 controls. The combined prevalence of autoimmune disease was higher among women (15.7% controls; 19.7% cases) than men (6.6% controls; 14.5% cases), but the overall association with NHL was stronger for men (odds ratio 2.4, 95% confidence interval: 1.53.8) than women (1.3, 0.91.9), the disparity persisting when data for the year immediately preceding lymphoma diagnosis were excluded (men 2.0, 1.33.3; women 1.2, 0.81.8). For both sexes, the strongest individual associations were for DLBCL, MZL and T-cell lymphomas, with no associations evident for FL. Among women, there were strong links between MZL and both Sjögren's syndrome and idiopathic thrombocytopenia, and among men, between DLBCL and both rheumatoid arthritis and Crohn's disease. The expected association between coeliac disease and T-cell lymphoma was seen in both sexes. Our results add to the accumulating knowledge on this topic and suggest that future studies should analyze data for men and women separately.
Assuntos
Doenças Autoimunes/epidemiologia , Disparidades nos Níveis de Saúde , Linfoma não Hodgkin/epidemiologia , Fatores Sexuais , Adolescente , Adulto , Idoso , Doenças Autoimunes/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Linfoma não Hodgkin/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Reino Unido/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Improvements in diagnostic approaches and refinements to treatment protocols have resulted in 5-year survival levels above 70% for children diagnosed with cancer in economically developed parts of the world. For some cancers, including leukaemia and tumours of the central nervous system, age and sex have been identified as important prognostic indicators. METHODS: We examined long-term survival, and affects of age and sex, in a population-based case-control study. Children (0-14 years) newly diagnosed with cancer were ascertained between 1991 and 1996 (n=4433). Follow-up information was obtained from the National Health Service (NHS) Information Centre for Health and Social Care which records all exits from the NHS including deaths. RESULTS: For all cancer diagnoses combined, 5-year survival was 72.7% dropping to 67.9% at 15 years. As expected, survival differed between diagnostic subtypes ranging from 38.1% for intracranial embryonal tumours to 96.2% for Hodgkin lymphoma. Compared to girls, boys diagnosed with acute lymphoblastic leukaemia were at a higher risk of dying (RR=1.26, 95% CI 1.03-1.53), whereas boys diagnosed with an intracranial embryonal tumour were at a lower risk of death (RR=0.63, 95% CI 0.43-0.91). CONCLUSION: Our initial findings are consistent with previous reports, and highlight the importance of considering differences by age and sex. The completeness and population-based nature of the original case-control study is an important feature which will provide the basis for future more detailed investigations linking disease determinants to outcome.
Assuntos
Neoplasias/epidemiologia , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias/diagnóstico , Neoplasias/patologia , Prognóstico , Fatores Sexuais , Taxa de Sobrevida , Reino Unido/epidemiologiaRESUMO
Studies of childhood leukemia and the potential etiologic role of genetic variation in folate metabolism have produced conflicting findings and have often been based on small numbers. We investigated the association between polymorphisms in key folate metabolism enzymes (MTHFR 677 C>T, MTHFR 1298 A>C, SHMT1 1420 C>T, MTR 2756 A>G, TS 1494del6, and TS 28bp repeat) in 939 cases of childhood acute lymphoblastic leukemia (ALL) and 89 cases of acute myeloid leukemia (AML) recruited into the United Kingdom Childhood Cancer Study. We also examined the maternal genotypes of 752 of these cases. Data from 824 noncancer controls recruited were used for comparison. No evidence of an association with MTHFR 677 was observed for ALL or AML, either in children or their mothers. However, in children an increased risk of ALL (odds ratio [OR] = 1.88; 95% confidence interval [CI], 1.16-3.07; P = .010) and AML (OR = 2.74; 95% CI, 1.07-7.01; P = .036) was observed with the MTR 2756 GG genotype; the association was most pronounced for cases with the MLL translocation (OR = 4.90; 95% CI, 1.30-18.45; P = .019). These data suggest that genetic variation in methionine synthase could mediate risk of childhood leukemia, either via effects on DNA methylation or via effects on fetal growth and development.
Assuntos
Ácido Fólico/metabolismo , Variação Genética/genética , Glicina Hidroximetiltransferase/genética , Leucemia Mieloide Aguda/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos de Casos e Controles , HumanosRESUMO
OBJECTIVE: To compare the frequency of brain tumor signs and symptoms in children with and without brain tumors. METHODS: This was a UK population-based retrospective analysis of primary care records. Participants were 195 children (1-14 years) newly diagnosed with brain tumors and 285 controls matched by age, gender, and region. Comparisons included total number of prediagnosis consultations, number with >or=1 symptom suggestive of a brain tumor, total number of symptoms, number of different symptoms, and number of visits with specific combinations of symptoms. RESULTS: On average, cases consulted more often than controls between birth and diagnosis/pseudodiagnosis with brain tumor signs and symptoms. Their consultation rate with >or=1 suggestive symptom escalated in the 2 years before diagnosis. Symptom prevalence was higher among cases than controls, a relative difference of 3.29 times as many consultations with >or=1 suggestive symptom (95% confidence interval [CI]: 2.82-3.83) and 7.01 as many with more than 1 (95% CI: 5.38-9.13). In each 6-month period in the 4 years before diagnosis, cases had at least twice as many consultations with >or=1 suggestive symptom (20.81 times as many in the 6 months before diagnosis [95% CI: 14.29-30.30]) and 2-3 times more records of suggestive symptoms (28.35 times more in the 6 months before diagnosis [95% CI: 19.05-42.19]). Symptoms rarely or not observed among control children included head tilt, odd head movements, odd posture, back or neck stiffness, and unsteadiness without obvious cause. CONCLUSION Key to identifying the 1 child among many who merits prompt investigation is recognition of unusual symptoms, or specific symptom patterns.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Detecção Precoce de Câncer/métodos , Atenção Primária à Saúde/normas , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Competência Clínica , Intervalos de Confiança , Testes Diagnósticos de Rotina , Feminino , Humanos , Incidência , Lactente , Masculino , Anamnese , Prontuários Médicos , Razão de Chances , Exame Físico , Atenção Primária à Saúde/tendências , Encaminhamento e Consulta/tendências , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Reino Unido/epidemiologiaRESUMO
Birth weight has been linked to the risk of developing childhood cancer, in particular childhood leukaemia. However, despite many childhood cancers having a male predominance and boys generally weighing more than girls at birth few studies have reported sex-specific associations. The relationship between birth weight and childhood cancer risk was examined using information from a national case-control study. Children (0-14 years) newly diagnosed with cancer in GB were ascertained between 1991 and 1996 (n=3651) and for comparison, controls matched on sex, month and year of birth were identified from primary care population registers (n=6337). Birth weights were obtained from the Office of National Statistics for all targeted subjects born in England and Wales. Overall, cases were, on average, 30 g heavier at birth than controls (p=0.003) with differences seen by cancer type; those diagnosed with hepatic tumours weighing around 500 g less than controls at birth (p<0.0001) and those with leukaemia being, on average, 50 g heavier than those without (p=0.001). An interaction between birth weight and sex was found for acute leukaemia (chi(2)=11.2, p=0.04) and when data were stratified by sex, an association between high birth weight and risk of ALL was seen with girls (>4000 g, OR 1.86, 95% CI 1.38-2.50, chi(2) for trend 20.2, p<0.0001). Our results support the hypothesis that birth weight is an important determinant for childhood cancer. In addition, the data are consistent with the notion that childhood leukaemia has a prenatal origin.
Assuntos
Peso ao Nascer/fisiologia , Neoplasias/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , História Antiga , Humanos , Recém-Nascido , Masculino , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Reino Unido/epidemiologiaRESUMO
We recently reported that two of six HLA-DP supertypes (DP1-4, 6, 8) were associated with susceptibility (DP2) and resistance (DP1) to childhood acute lymphoblastic leukaemia (ALL). To determine whether DP supertypes are associated with childhood ALL prognosis, we compared treatment outcomes in a cohort (n = 798) of DPB1-typed ALL cases in the UK Medical Research Council UKALL XI trial. No differences in clinical characteristics and outcome between DPB1-typed and untyped (n = 1292) cases suggest no selection bias. Event-free survival (EFS) rates in patients with DP1 and DP3 supertypes were significantly worse than in patients with DP2, DP4, DP6 and DP8 [10-year EFS: 55%; 95% confidence interval (CI) = 49-61%; compared with 64% (61-68%), P = 0.006]. Ten-year EFS in DP1/DP3 heterozygous patients [30% (2-58%)] was significantly worse than in patients with DP1, DP3 or neither allele [56% (50-62%); P = 0.02]. Lack of evidence that DP1 or DP3 are associated with known prognostic factors leads us to suggest that these two supertypes exert an independent effect on prognosis. This may involve abrogation of DP1/3-restricted T-cell control of residual disease due to selective effects of chemotherapy. Further studies of HLA supertypes in relation to outcome in recent childhood ALL trials may resolve this question.