Nearly 12,400 children and adolescents under the age of twenty years will be newly diagnosed with cancer each year in the United States. This means that a newborn has an approximately 1 in 315 chance of developing cancer in the first two decades of life. This chapter reviews the epidemiology of cancer in children. Topics covered include overall incidence, mortality and morbidity, acute lymphoblastic leukemia and acute myeloid leukemia, brain/central nervous system cancers, lymphomas, sympathetic nervous system tumors, soft tissue sarcoma, renal cancers, bone tumors, germ cell tumors, retinoblastoma, and hepatic tumors. © 2006 by Oxford University Press, Inc. All rights reserved.

OBJECTIVE: The risk of hepatoblastoma is strongly increased among children with very low birth weight (<1500 g). Because data on very low birth weight and other childhood cancers are sparse, we examined the risk of malignancy with very low birth weight in a large data set. METHODS: We combined case-control data sets created by linking the cancer and birth registries of California, Minnesota, New York, Texas, and Washington states, which included 17672 children diagnosed as having cancer at 0 to 14 years of age and 57966 randomly selected control subjects. Unconditional logistic regression analysis was used to examine the association of cancer with very low birth weight and moderately low birth weight (1500-1999 g and 2000-2499 g, respectively), compared with moderate/high birth weight (>or=2500 g), with adjustment for gender, gestational age, birth order, plurality, maternal age, maternal race, state, and year of birth. RESULTS: Most childhood cancers were not associated with low birth weights. However, retinoblastomas and gliomas other than astrocytomas and ependymomas were possibly associated with very low birth weight. The risk of other gliomas was also increased among children weighing 1500 to 1999 g at birth. CONCLUSIONS: These data suggested no association between most cancers and very low birth weight, with the exception of the known association of hepatoblastoma and possibly moderately increased risks of other gliomas and retinoblastoma, which may warrant confirmation.

BACKGROUND: Children with Down syndrome (DS) have about a 20-fold increased risk of developing leukemia. Early childhood infections may protect against acute lymphoid leukemia (ALL) in children with and without DS. We examined whether maternal infections and health conditions during pregnancy were associated with acute leukemia in children with DS.\n\nPROCEDURE: We conducted a case-control study of 158 children with DS and leukemia (including 97 cases with acute lymphoblastic leukemia (ALL) and 61 cases with acute myeloid leukemia (AML)) and 173 children with DS during the period 1997-2002. Maternal interview included information about 14 maternal conditions during gestation that are likely to induce an inflammatory response. We evaluated their prevalence in cases and controls. Five of these were common enough to allow analyses by leukemia subtype.\n\nRESULTS: Vaginal bleeding was the most frequent (18% cases, 25% controls) and was associated with a reduced risk (odds ratio (OR) = 0.57; 95% confidence interval (CI) = 0.33-0.99) for all cases combined. Other variables, while showing a potential trend toward reduced risk had effect estimates, which were imprecise and not statistically significant. In contrast, amniocentesis was marginally associated with an increased risk of AML (OR = 2.06, 95% CI = 0.90-4.69).\n\nCONCLUSIONS: Data from this exploratory investigation suggest that some health conditions during pregnancy may be relevant in childhood leukemogenesis. Larger epidemiological studies and other model systems (animal, clinical studies) may provide a clearer picture of the potential association and mechanisms.

BACKGROUND Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. METHODS We assessed the relationship between parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0-14 years during 1980-2004 and 57,966 controls born during 1970-2004. Individuals with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. RESULTS Positive linear trends per 5-year maternal age increase were observed for childhood cancers overall (odds ratio = 1.08 [95% confidence interval = 1.06-1.10]) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 [1.05-1.11]), lymphoma (1.06 [1.01-1.12]), central nervous system tumors (1.07 [1.03-1.10]), neuroblastoma (1.09 [1.04-1.15]), Wilms' tumor (1.16 [1.09-1.22]), bone tumors (1.10 [1.00-1.20]), and soft tissue sarcomas (1.10 [1.04-1.17]). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. CONCLUSIONS Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.

Traditionally, controls in US pediatric cancer studies were selected through random digit dialing. With declining participation and lack of nonparticipant information, random digit dialing (RDD) controls may be substandard. Birth certificate (BC) controls are an alternative, because they are population based and include data from nonparticipants. The authors examined controls collected by random digit dialing and birth certificates for a Children's Oncology Group case-control study of infant leukemia in 1995-2006. Demographic variables were used to assess differences in RDD and BC controls and their representativeness. RDD and BC controls did not differ significantly with regard to maternal variables (age, race, education, marital status, alcohol during pregnancy) or child variables (sex, gestational age, birth weight), but they varied in smoking during pregnancy (22% RDD controls, 12% BC controls) (P = 0.05). The study's combined control group differed significantly from US births: Mothers of controls were more likely to be older (29.8 vs. 27.2 years), white (84% vs. 59%), and married (85% vs. 67%) and to have >16 years of education (37% vs. 25%). Control children were more often full term (88% vs. 81%) and heavier (3,436 vs. 3,317 g). Finally, participating BC mothers were likely to be older and to have more education than nonparticipants. Thus, the study's control groups were comparable but differed from the population of interest.

Although several studies have found no change or a decreased risk of childhood cancer in twins, few have controlled for potential confounders such as birth weight. We examined the association of birth plurality and childhood cancer in pooled data from five U.S. states (California, Minnesota, New York, Texas, and Washington) using linked birth-cancer registry data. The data, excluding children with Down syndrome or who died before 28 days of life, included 17,672 cases diagnosed from 1980 to 2004 at ages 28 days to 14 years and 57,966 controls with all cases and controls born from 1970 to 2004. Analyses were restricted to children weighing <or=4,000 g at birth. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression adjusting for sex, gestational age, birth weight, birth order, maternal age, maternal race, state of birth, and birth year. Children who were multiples had no difference in risk of cancer overall (OR, 0.93; 95% CI, 0.82-1.07), but a borderline reduced risk of Wilms' tumor (OR, 0.65; 95% CI, 0.39-1.09). For children diagnosed <2 y of age there was a reduced risk of Wilms' tumor (OR, 0.27; 95% CI, 0.09-0.86) and neuroblastoma (OR, 0.46; 95% CI, 0.25-0.84) and an increased risk of fibrosarcoma (OR, 5.81; 95% CI, 1.53-22.11). Higher-order multiple birth (triplets or higher) was not associated with childhood cancer. Our analysis suggests that mechanisms other than birth weight and gestational age may influence the lower risk of Wilms' tumor and neuroblastoma in multiple births.

BACKGROUND: Recent studies in childhood cancer suggest that maternal vitamin supplementation may reduce the risk of leukaemia, neuroblastoma and certain types of childhood brain tumours. For example, a previous study found a significantly reduced risk of acute lymphoblastic leukaemia (ALL) but not acute myeloid leukaemia (AML) in children with Down syndrome whose mothers reported any vitamin supplement use prior to knowledge of pregnancy (ALL OR adjusted for confounders 0.51, 95% confidence limits (CL): 0.30, 0.89; AML OR adjusted for confounders 0.92, 95% CL 0.48, 1.76). Recall of exposures, including maternal vitamin supplement use, however, may be difficult and subject to error. Epidemiologists are encouraged to quantitatively adjust for systematic error in study results, but often do not. METHODS: The impact that misclassification of maternal vitamin supplement use may have had on the observed ORs in this study was quantified. Uncertainty analysis was used to calculate ORs adjusted for inaccurate reporting of vitamin supplement use under assumed probability distributions for exposure misclassification parameters. RESULTS: Given our assumptions, adjustment for exposure misclassification yielded ORs that were predominantly more protective for ALL than the crude OR. CONCLUSIONS: Uncertainty analysis can give important insights into the magnitude and direction of error in study results due to exposure misclassification.

Objective: To determine whether the postnatal growth rate of infants with intrauterine growth restriction (IUGR) is associated with later cognitive function and body mass index (BMI). Study design: Infants with IUGR (<2211 g at ≥37 weeks' gestation) were identified in data from the Collaborative Perinatal Project, excluding those with diagnoses affecting cognition or growth. Wechsler Scale of Children's Intelligence (WISC) scores at age 7 years and data on postnatal growth at 16 weeks were available for 463 infants with IUGR. Linear regression relating postnatal growth and WISC score, adjusting for potential confounders, was performed for these infants. BMI at 7 years also was examined. Results: Weight gain at 16 postnatal weeks ranged from 1059 to 5119 g in the infants with IUGR, with lower achieved cognitive testing scores apparent at both extremes (ie, an inverted J-shape; P < .001). Infants gaining 1200 and 5000 g scored 15.5 and 2.4 fewer points, respectively, on the full scale compared with infants with score-maximizing growth. In contrast, BMI at 7 years was linearly related to postnatal weight gain (P < .001). Conclusions: Growth in the first 4 postnatal months is an independent risk factor for cognitive outcome at age 7 years, with both extremes associated with negative effects. © 2009 Mosby, Inc. All rights reserved.

Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL), few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology.

We confirmed the strong association of hepatoblastoma with very low birth weight (relative risk <1000 g vs >or=2000 g=25.6; 95% confidence interval: 7.70-85.0) and demonstrated independent associations with congenital abnormalities and maternal Asian race in a population-based Minnesota study that included 36 cases and 7788 controls.

More than 13,000 children are estimated to be newly diagnosed with cancer each year in the United States ([1][1]). Despite substantial improvements in survival over the last several decades, cancer is still the leading cause of death due to disease in children ages 1 to 14 years ([2][2]). The

Wilms tumor (WT) is a childhood kidney cancer with the highest rate of occurrence before the age of 2. Since it is rare, previous research has been limited and few risk factors have been established. We used a case-cohort design to examine the influence of birth characteristics on occurrence of WT in Minnesota. A total of 2,188 cases of cancer diagnosed in children aged 28 days to 14 years from 1988 to 2004 were identified using the Minnesota Cancer Surveillance System (MCSS). For each case, 4 children were randomly selected from Minnesota birth records during 1976-2004, frequency matched on birth year. Thus, a total of 8,752 children comprised the subcohort for the study, who in this analysis, served as comparison to the 138 cases of WT. Study variables included parental demographics, maternal pregnancy history and conditions and health and conditions of the child at birth. Associations with WT were assessed using hazard ratios (HR) and 95% confidence intervals (CI) calculated from stratified Cox regression models. We found an increased risk of WT for children who were large for gestational age compared to those average for gestational age and for children with congenital abnormalities. There was also an increased risk for children with a birth weight > 4,000 g compared to those with a birth weight between 2,500 and 4,000 g. All other factors examined showed no association with WT. This study contributes to the mounting evidence that children with large size at birth have an increased risk of WT.

A comprehensive case-control study was conducted to evaluate parental\nrisk factors for medulloblastoma (MB) and primitive neuroectodermal\ntumor (PNET). This analysis was conducted to evaluate associations\nbetween fathers' hobbies and risk of their children developing MB/PNET.\nThe hobbies chosen for study were those with similar exposures as\noccupations associated with childhood cancers.\nCases were 318 subjects under six years of age at diagnosis between 1991\nand 1997 and registered with the Children's Cancer Group. An equal\nnumber of controls were selected through random digit dialing and\nindividually matched to cases.\nIn multivariate analyses, a significant association was seen for lawn\ncare with pesticides {[}during pregnancy: odds ratio (OR) = 1.6, 95%\nconfidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2,\n2.8] and a weak association was seen for stripping paint {[}during\npregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI:\n0.7, 2.6].\nThis study suggests that household exposures from hobbies, particularly\npesticides, may increase risk of MB/PNET in children; previous research\nhas been mostly limited to occupational exposures.

We examined the risk of childhood cancer (<20 years) among 105 950 offspring born in 1921-1984 to US radiologic technologist (USRT) cohort members. Parental occupational in utero and preconception ionising radiation (IR) testis or ovary doses were estimated from work history data, badge dose data, and literature doses (the latter doses before 1960). Female and male RTs reported a total of 111 and 34 haematopoietic malignancies and 115 and 34 solid tumours, respectively, in their offspring. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Leukaemia (n=63) and solid tumours (n=115) in offspring were not associated with maternal in utero or preconception radiation exposure. Risks for lymphoma (n=44) in those with estimated doses of <0.2, 0.2-1.0, and >1.0 mGy vs no exposure were non-significantly elevated with HRs of 2.3, 1.8, and 2.7. Paternal preconception exposure to estimated cumulative doses above the 95th percentile (82 mGy, n=6 cases) was associated with a non-significant risk of childhood cancer of 1.8 (95% CI 0.7-4.6). In conclusion, we found no convincing evidence of an increased risk of childhood cancer in the offspring of RTs in association with parental occupational radiation exposure.

Neuroblastoma (NB), a tumor of the sympathetic nervous system, is the most common infant malignancy. The etiology of NB is largely unknown. We explored the association between birth record variables and subsequent NB development in a population-based case-cohort study in Minnesota by linking the birth and cancer registries. NB cases included 155 children born during 1976-2004 who were diagnosed from 28 days through 14 years of age. The comparison group included 8,752 individuals randomly sampled from the birth cohort of cases. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Controlling for birth year and sex, maternal history of one fetal loss (HR = 1.7, 95% CI 1.2-2.5), maternal prenatal drug-use (recorded starting in 1992) (HR = 5.7, 95% CI 2.3-14) and child's small size for gestational age (HR = 2.1, 95% CI 1.1-4.0) were significantly associated with NB. Age group specific analyses indicated that maternal hypertension (HR = 3.0, 95% CI 1.3-7.2) and maternal age <20 years (HR = 2.6, 95% CI 1.1-6.1) increased risks for infant NB only. Our study provides evidence that a few perinatal exposures as recorded in birth records may play a role in NB etiology.

Since the mid-1990s, epidemiologists have anecdotally reported difficulty in recruiting controls using random digit dialing (RDD), but few empirical data have been published. From 1982 to 2003, epidemiologists from the Children's Oncology Group conducted 17 case-control studies using RDD controls. Data for calculating RDD and field response rates were available from eight and 13 of these studies, respectively. Over the period of analysis, the contact rate declined 2.5% per year (95% confidence interval (CI): -3.4, -1.6; p = 0.001), from above 90% in the 1980s to 63-69% in the most recent studies. The response rate (the product of the contact and cooperation rates) showed a decline parallel to that of the contact rate (-2.4% per year, 95% CI: -3.2, -1.6; p < 0.001), from above 80% in the 1980s to 50-67% after the mid-1990s. Field response rates appeared to have declined modestly. The overall response rate (the product of the RDD response and field response rates) paralleled that of the RDD response rate and decreased 2.4% per year (95% CI: -2.7, -2.0; p < 0.001). The current low response rates for RDD indicate a substantial potential for selection bias and a need to seek alternative sources of controls.