Summary The causes of childhood cancer have been systematically studied for several decades, but apart from high-dose radiation and prior chemotherapy there are few or no strong external risk factors. On the other hand, inherent risk factors including birth weight, parental age, and congenital anomalies are consistently associated with most types of pediatric cancer. Rare, highly-penetrant syndromes have long been known to cause a small proportion of cancers but recently the contribution of common genetic variation to etiology has come into focus through genome wide association studies. These have highlighted genes not previously implicated in childhood cancers and, surprisingly, have suggested that common variation explains a larger proportion of childhood cancers than adult. Rare variation and non-Mendelian inheritance, such as through maternal genetic effects or de novo germline mutations, may also contribute to childhood cancer risk but have not been widely examined to date.

SummaryBackground-Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery.

Betel quid chewing is likely contributing to high blood pressure in Bangladesh, particularly among women.

Background Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from Cancer Incidence in 5 Continents (CI5) from 1988 to 2012 (CI5 volumes VII–XI). Methods Rates of cancers in children ages 0–4 years were extracted from registries available in CI5 from 1988 to 2012. To overcome small numbers in individual registries, numerators and denominators were aggregated within regions corresponding to the United Nations’ geoscheme. Average annual percent change (AAPC) was estimated using Poisson regression.  Robust standard errors were used in all models to correct for overdispersion in some regions, and 95% Wald confidence intervals and P values were reported. The top five cancers by increasing AAPC were ranked within each region. Results Overall, in children under 5 years, increasing incidence was seen in multiple regions for acute lymphoblastic leukemia, acute myeloid leukemia, ependymal tumors, neuroblastoma, and hepatoblastoma. Hepatoblastoma had the largest AAPC in 11 out of 15 regions and showed an increase in all regions except southern Asia. Astrocytic tumors were the only cancer that decreased over the time period. Conclusions We evaluated 25 years of cancer incidence in children ages 0–4 years and observed increases in incidence for hepatoblastoma, leukemia, neuroblastoma, and ependymal tumors. Further etiologic evaluation will be required to explain these increases in incidence.

Background The male excess in childhood cancer incidence is well‐established; however, the underlying biologic mechanisms remain unknown. Examining the association between male sex and childhood cancer by single year of age and tumor type may highlight important periods of risk such as variation in growth and hormonal changes, which will inform etiologic hypotheses. Methods Using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2000–2015), incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated as the measure of association between male sex and childhood cancer by single year of age (0–19). Results The IRR for male cancer overall was 1.19 (95% CI, 1.18–1.20) and was similar in magnitude at nearly every year of age. Burkitt lymphoma was strongly associated with male sex (IRRs ≥2 at each year of age). Increased incidence was observed among males for acute lymphoblastic leukemia, Hodgkin and non‐Hodgkin lymphomas for nearly all years of age. Medulloblastoma was the only central nervous system tumor with a significant male predominance at nearly every age. Male sex displayed a consistent inverse association with nephroblastoma and thyroid carcinoma over the ages studied. Conclusions Male sex was positively associated with most cancers. The higher incidence rates observed in males remained consistent over the childhood and adolescent periods, suggesting that childhood and adolescent hormonal fluctuations may not be the primary driving factor for the sex disparities in childhood cancer. The observed incidence disparities may be due to sex differences in exposures, genetics, or immune responses.

Background Epidemiologic studies indicate that infections in early childhood may protect against pediatric acute lymphoblastic leukemia (ALL). Methods We identified 3,402 ALL cases among children 0–5 years using the California Cancer Registry. From California birth records we randomly selected controls in a 20:1 ratio and frequency matched them to cases by birth year. We investigated markers of exposure to infections, including month of birth, timing of birth in relation to influenza and respiratory syncytial virus (RSV) seasons, and birth order based on data from California birth certificates and national infection surveillance systems. Results We observed an increased risk of ALL for spring and summer births, and for those first exposed to an influenza or RSV season at nine to twelve months of age compared to those exposed during the first three months of life, and this association was stronger among first born children (OR and 95% CI 1.44 [1.13, 1.82] for influenza exposure at nine to twelve months of age). Decreased risk was observed with increasing birth order among non-Hispanic whites but not Hispanics (OR and 95% CI 0.76 [0.59, 096] for fourth or higher birth order among whites). Conclusion Our results support the hypothesis that infections in early childhood decrease risk of ALL. Impact Our findings implicate early life exposure to infections as protective factors for ALL in young children.

Childhood leukemias are heterogeneous diseases with widely differing incident rates worldwide. As circulating tumors, childhood acute leukemias are uniquely accessible, and their natural history has been described in greater detail than for solid tumors. For several decades, it has been apparent that most cases of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) initiate in utero. Circumstantial evidence in support of this contention includes the young age of onset and high rate of concordance among identical twins. “Backtracking” of leukemic somatic mutations, particularly gene translocations, to cord blood and dried blood spots collected during the perinatal period has provided molecular proof of prenatal leukemogenesis. Detection of a patient's leukemia translocation in easily accessible birth samples, such as dried blood spots, is straightforward with the knowledge of their idiosyncratic breakpoints. However, to translate these findings into population-based screening and leukemia prevention requires novel methods able to detect translocations at all possible breakpoints when present in a low frequency of cells. Several studies have attempted to screen for leukemic translocations, mainly the common ETV6-RUNX1 translocation, in cord blood samples from healthy children. Most studies have reported finding translocations in healthy children, but estimates of prevalence have varied widely and greatly exceed the incidence of leukemia, leading to concerns that technical artifact or contamination produced an artificially inflated estimate of translocation prevalence at birth. New generation techniques that capture the presence of these translocations at birth have the potential to vastly increase our understanding of the epidemiology of acute leukemias. For instance, if leukemic translocations are present at birth in a far higher proportion of children than eventually develop acute leukemia, what are the exposures and somatic molecular events that lead to disease? And could children with translocations present at birth be targeted for prevention of disease? These questions must be answered before large-scale newborn screening for leukemia can occur as a public health initiative. Here, we review the literature regarding backtracking of acute leukemias and the prevalence of leukemic translocations at birth. We further suggest an agenda for epidemiologic research using new tools for population screening of leukemic translocations.

BACKGROUND:Incidence rates of pediatric cancers in the United States are typically reported in 5-year age groups, obscuring variation by single year of age. Additionally, racial and ethnic variation in incidence is typically presented in broad categories rather than by narrow age ranges. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 18 data (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) were examined to calculate frequencies and age-adjusted incidence rates among individuals aged birth to 39 years. Incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) were estimated as the measure of association for rate comparisons by race and Hispanic origin overall and by single year of age. RESULTS: Several histologic types showed substantial variation in race/ethnicity-specific and overall rates by single year of age. Overall, Black children and young adults experienced substantially decreased incidence of acute lymphoid leukemia (IRR, 0.52; 95% CI, 0.49-0.55) compared to Whites, and this decreased incidence was strongest at ages 1 through 7 years and 16 through 20 years. Hispanic individuals experienced decreased overall incidence of Hodgkin lymphoma (IRR, 0.50; 95% CI, 0.48-0.52) and astrocytoma (IRR, 0.54; 95% CI, 0.52-0.56) and increased risk of acute lymphoblastic leukemia (IRR, 1.46; 95% CI, 1.42-1.51) compared to non-Hispanic Whites, and the increased risk was strongest at ages 10 through 23 years. Substantial decreased risk across many tumor types was also observed for Asian/Pacific Islanders and American Indian/Alaska Natives. CONCLUSIONS: Examination of incidence rates for pediatric cancers by narrow age groups may provide insights regarding etiological differences in subgroups. Additionally, variation in age-specific incidence rates by race and ethnicity may enable hypothesis generation on drivers of disparities observed.