Incidence of and survival from childhood cancer : the role of social and family factors in childhood cancer

Introduction: Social inequalities, both within countries and between countries, influence the occurrence of and survival from cancer, including childhood cancer. This dissertation aimed to gain further insight into social inequalities in childhood cancer â on the national level within a country and also between countries with different levels of socioeconomic development. The first objective was to obtain a better understanding of the reported geographical differences in childhood cancer worldwide by studying incidence patterns in a Sub-Saharan African country (with a diverse racial/ethnic population) and comparing the findings to the incidence patterns of a representative high-income country (Germany). The second objective was to investigate survival from childhood cancers in relation to social and family factors within high-income countries. Methods: The two objectives were addressed by seven conceptually independent but topic-wise interrelated studies. Four studies provided the core manuscripts for this thesis: i) childhood cancer incidence patterns by race in South Africa, and in comparison to Germany; ii) survival from acute lymphoblastic leukaemia (ALL) in relation to socio-demographic background in Germany; iii) survival from ALL in relation to family factors in Germany; iv) survival from childhood haematological malignancies in relation to family factors in Denmark. Data from the South African National Cancer Registry, the German Childhood Cancer Registry, a former German case-control study, as well as from the Danish registries served as the basis for these studies. The incidence data were analysed by applying descriptive epidemiological methods. Kaplan-Meier curves and Cox proportional hazard models were used for the survival analyses. Results: Substantial differences in the reported incidence rates were observed within South African racial groups, with lowest rates among Black children and highest among White children. There were also considerable differences between White children in South Africa and in Germany, but the differences varied markedly by cancer type and by age at diagnosis. Social and family characteristics were found to be associated with survival from childhood cancers, although not consistently between Germany and Denmark and not across cancer types. An impact of socioeconomic factors on survival from ALL was not observed for either Germany or Denmark, however a beneficial effect of higher maternal education among children with non-CNS solid tumours in Denmark was observed. Higher birth order and having siblings was associated with poorer survival among childhood haematological cancer patients in Denmark, with associations being suggestive for ALL and non-Hodgkin lymphoma but stronger and statistically significant for acute myeloid leukaemia. Similarly, most associations with family factors were suggestive for survival from ALL in German children. Highest survival in Germany was seen for second-born children. Patterns of associations between parental age and survival from childhood cancers were diverse across studies. Discussion: Findings of this dissertation highlight social inequalities in childhood cancer with respect to reported incidence differences between racial groups in South Africa and compared to Germany. Furthermore, survival differences between social groups in Germany and Denmark were observed, although not consistently across cancer types. To reduce those observed social inequalities in childhood cancer, a thorough understanding of the underlying mechanisms and pathways is needed. Observed incidence differences in South Africa might be, at least to some extent, due to socio-cultural factors related to access and utilization of health care services rather than reflecting actual differences in cancer risks. Under-ascertainment of cases may not only drive the findings for South Africa but the global reported geographical patterns of childhood cancer incidence. Despite highly specialized and standardised treatment and free health services for all children in Germany and Denmark, not all children benefit equally from improvements in childhood cancer survival. Further studies are warranted to gain knowledge on the impact of social and family factors on childhood cancer survival in other populations and to identify underlying pathways

Social Inequalities Along the Childhood Cancer Continuum: An Overview of Evidence and a Conceptual Framework to Identify Underlying Mechanisms and Pathways

Inequalities in health according to social conditions are regarded as unnecessary and unjust. There is a large body of evidence on inequalities in adult cancer, observable throughout the societies on a national level as well as on a global scale. Socioeconomic influences on health matter at all ages including childhood, for which childhood cancer is the leading cause of disease related death in high-income countries (HICs). Substantial differences in the reported incidence of childhood cancers have been observed globally by socioeconomic development of a population. This is reflected in the higher incidence rates reported for HICs, particularly for acute lymphoblastic leukemia, and for cancer in infants (below 1 year), compared to low- and middle-income countries (LMICs). Considerable inequalities between populations and degree of socioeconomic development are also noted for survival from childhood cancer, with substantially lower survival rates seen in most LMICs compared to HICs. With respect to inequalities by socioeconomic position (SEP) within countries, findings of an association between SEP and childhood cancer risk are diverse and limited to studies from HICs. On the contrary, observations on social inequalities in survival within countries are accumulating and indicate that survival inequalities do not only concern resource-poor countries but also high-income populations including European countries. In turn, a childhood cancer diagnosis in itself may have implications on the parents' socioeconomic situation as well as on the later socioeconomic life after having survived the disease. The underlying mechanisms and causal pathways of these empirically demonstrated social inequalities are poorly understood, although it is of significant public health relevance for any actions or strategies to reduce childhood cancer-related inequity. We propose a conceptual framework on potential underlying mechanism and pathways specifically addressing social inequalities in childhood cancer and after childhood cancer to (i) illustrate potential pathways by which social determinants may create health inequities at different points of the childhood cancer continuum; (ii) illustrate potential pathways by which a childhood cancer diagnosis may impact the socioeconomic situation of the concerned family or the later life of a childhood survivor; and (iii) point out how major determinants may relate to each other

Childhood and adolescent cancer in Germany – an overview

Background: Childhood and adolescent cancer constitutes only a very small fraction of the cancer cases in Germany and throughout the world, but it is the most frequent cause of disease-related death in children. The diagnostic spectrum differs markedly from that of adults. More than 90% of all cases of childhood and adolescent cancer in Germany are treated according to centralised protocols or in therapy studies. Methods: The main epidemiological data for this group are collected by the German Childhood Cancer Registry (GCCR) since 1980. Based on this data, three typical diagnoses and their incidence and prognosis are described in exemplary manner: Lymphoid leukaemia (LL), astrocytoma and neuroblastoma. Results: Approximately 2,250 new cancers are diagnosed in children and adolescents under the age of 18 in Germany every year. In this age group, leukaemia and lymphoma account for almost 50% of all new cancer cases, predominately acute forms. Overall, the prognosis is considerably better than in adults. Conclusions: There is relatively little consistent evidence available on external factors as risk factors for childhood cancer, despite decades of research. For LL, the immune system and infections are assumed to play a role, as early training of the immune system appears to be protective. To an increasing degree, research is identifying genetic risk factors for many types of childhood and adolescent cancer. The therapy is sometimes very intensive and leads to a variety of late effects for at least 75% of the survivors, which may occur soon after the primary diagnosis, but also decades later

Survival After Childhood Cancer–Social Inequalities in High-Income Countries

Despite substantial improvements in survival from childhood cancer during the last decades, there are indications that survival rates for several cancer types are no longer improving. Moreover, evidence accumulates suggesting that socioeconomic and sociodemographic factors may have an impact on survival also in high-income countries. The aim of this review is to summarize the findings from studies on social factors and survival in childhood cancer. Several types of cancer and social factors are included in order to shed light on potential mechanisms and identify particularly affected groups. A literature search conducted in PubMed identified 333 articles published from December 2012 until June 2018, of which 24 fulfilled the inclusion criteria. The findings are diverse; some studies found no associations but several indicated a social gradient with higher mortality among children from families of lower socioeconomic status (SES). There were no clear suggestions of particularly vulnerable subgroups, but hematological malignancies were most commonly investigated. A wide range of social factors have been examined and seem to be of different importance and varying between studies. However, potential underlying mechanisms linking a specific social factor to childhood cancer survival was seldom described. This review provides some support for a relationship between lower parental SES and worse survival after childhood cancer, which is a finding that needs further attention. Studies investigating predefined hypotheses involving specific social factors within homogenous cancer types are lacking and would increase the understanding of mechanisms involved, and allow targeted interventions to reduce health inequalities

Social Inequalities Along the Childhood Cancer Continuum:An Overview of Evidence and a Conceptual Framework to Identify Underlying Mechanisms and Pathways

Inequalities in health according to social conditions are regarded as unnecessary and unjust. There is a large body of evidence on inequalities in adult cancer, observable throughout the societies on a national level as well as on a global scale. Socioeconomic influences on health matter at all ages including childhood, for which childhood cancer is the leading cause of disease related death in high-income countries (HICs). Substantial differences in the reported incidence of childhood cancers have been observed globally by socioeconomic development of a population. This is reflected in the higher incidence rates reported for HICs, particularly for acute lymphoblastic leukemia, and for cancer in infants (below 1 year), compared to low- and middle-income countries (LMICs). Considerable inequalities between populations and degree of socioeconomic development are also noted for survival from childhood cancer, with substantially lower survival rates seen in most LMICs compared to HICs. With respect to inequalities by socioeconomic position (SEP) within countries, findings of an association between SEP and childhood cancer risk are diverse and limited to studies from HICs. On the contrary, observations on social inequalities in survival within countries are accumulating and indicate that survival inequalities do not only concern resource-poor countries but also high-income populations including European countries. In turn, a childhood cancer diagnosis in itself may have implications on the parents' socioeconomic situation as well as on the later socioeconomic life after having survived the disease. The underlying mechanisms and causal pathways of these empirically demonstrated social inequalities are poorly understood, although it is of significant public health relevance for any actions or strategies to reduce childhood cancer-related inequity. We propose a conceptual framework on potential underlying mechanism and pathways specifically addressing social inequalities in childhood cancer and after childhood cancer to (i) illustrate potential pathways by which social determinants may create health inequities at different points of the childhood cancer continuum; (ii) illustrate potential pathways by which a childhood cancer diagnosis may impact the socioeconomic situation of the concerned family or the later life of a childhood survivor; and (iii) point out how major determinants may relate to each other

Socioeconomic differences in the risk of childhood central nervous system tumors in Denmark:a nationwide register-based case–control study

Purpose!#!Differences in the risk of childhood central nervous system (CNS) tumors by socioeconomic status (SES) may enhance etiologic insights. We conducted a nationwide register-based case-control study to evaluate socioeconomic differences in the risk of childhood CNS tumors in Denmark and examined whether associations varied by different SES measures, time points of assessment, specific tumor types, and age at diagnosis.!##!Methods!#!We identified all children born between 1981 and 2013 and diagnosed with a CNS tumor at ages 0-19 years (n = 1,273) from the Danish Cancer Registry and sampled four individually matched controls per case (n  = 5,086). We used conditional logistic regression models to estimate associations with individual-level and neighborhood-level socioeconomic measures.!##!Results!#!We observed elevated risks of ependymoma and embryonal CNS tumors in association with higher parental education (odds ratios (ORs) of 1.6-2.1 for maternal or paternal high education and ependymoma) and higher risk of all tumor types in association with higher maternal income, e.g., OR  1.93; 95% CI 1.05-3.52 for high versus low income for astrocytoma and other gliomas. Associations were often stronger in children diagnosed at ages 5-19 years. We found little evidence for an association with neighborhood SES.!##!Conclusion!#!This large nationwide register study with minimal risk of bias showed that having parents with higher educational level and a mother with higher income was associated with a higher risk of childhood CNS tumors. Bias or under-ascertainment of cases among families with low income or basic education is unlikely to explain our findings

Number of siblings and survival from childhood leukaemia : a national register-based cohort study from Sweden

Background: Previous studies suggest worse leukaemia survival for children with siblings, but the evidence is sparse, inconsistent and does not consider clinical factors. We explored the associations between number of siblings in the household, birth order, and survival from childhood acute lymphoid leukaemia (ALL) and acute myeloid leukaemia (AML). Methods: In this nationwide register-based study we included all children aged 1-14, diagnosed with ALL and AML between 1991-mid 2015 in Sweden (n=1692). Using Cox regression models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) according to number of siblings and birth order, adjusting for known prognostic and sociodemographic factors. Results: A tendency towards better ALL survival among children with one, or ≥2, siblings was observed, adjHRs (95% CI): 0.73 (0.49-1.10) and 0.63 (0.40-1.00), respectively. However, this was mainly limited to children with low risk profiles. An indication of better AML survival among children with siblings was seen, adjHRs (95% CI) 0.68 (0.36-1.29) and 0.71 (0.34-1.48) but diminished after adjusting for birth order. Conclusion: Our results do not support previous findings that a larger number of siblings is associated with poorer survival. Inconsistencies might be explained by underlying mechanisms that differ between settings, but chance cannot be ruled out.The Swedish Research Council for Health, Working Life and Welfare (contract no. 2013-1072)Accepte

Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care