Racial and ethnic and socioeconomic disparities in childhood cancer incidence trends in the United States, 2000-2019.

BACKGROUND: Population-based surveillance of pediatric cancer incidence trends is critical to determine high-risk populations, drive hypothesis generation, and uncover etiologic heterogeneity. We provide a comprehensive update to the current understanding of pediatric cancer incidence trends by sex, race and ethnicity, and socioeconomic status (SES). METHODS: The Surveillance, Epidemiology, and End Results 22 data (2000-2019) was used to summarize age-adjusted incidence rates for children and adolescents aged 0-19 years at diagnosis. The annual percentage change (APC) and 95% confidence interval (CI) were estimated to evaluate incidence trends by sex, race and ethnicity, and SES overall and for cancer subtypes. Tests of statistical significance were 2-sided. RESULTS: Substantial variation was observed overall and for several histologic types in race and ethnicity- and SES-specific rates. Overall, we observed a statistically significant increase in incidence rates (APC = 0.8%, 95% CI = 0.6% to 1.1%). All race and ethnic groups saw an increase in incidence rates, with the largest occurring among non-Hispanic American Indian and Alaska Native children and adolescents (APC = 1.7%, 95% CI = 0.5% to 2.8%) and the smallest increase occurring among non-Hispanic White children and adolescents (APC = 0.7%, 95% CI = 0.5% to 1.0%). The lowest SES quintiles saw statistically significant increasing trends, while the highest quintile remained relatively stable (quintile 1 [Q1] APC = 1.6%, 95% CI = 0.6% to 2.6%; quintile 5 [Q5] APC = 0.3%, 95% CI = -0.1% to 0.7%). CONCLUSIONS: Childhood cancer incidence is increasing overall and among every race and ethnic group. Variation by race and ethnicity and SES may enable hypothesis generation on drivers of disparities observed.

Maternal Body Mass Index, Diabetes, and Gestational Weight Gain and Risk for Pediatric Cancer in Offspring: A Systematic Review and Meta-Analysis.

BACKGROUND: Pediatric cancer incidence has steadily increased concurrent with rising adult obesity, but associations between maternal obesity and associated comorbidities and pediatric cancer risk remain understudied. We aimed to quantitatively characterize associations of pediatric cancer risk with maternal prepregnancy body mass index (BMI), gestational weight gain, and maternal diabetes. METHODS: We performed a comprehensive and systematic literature search in Ovid and EMBASE from their inception to March 15, 2021. Eligible studies reported risk estimates and sample sizes and provided sufficient description of outcome and exposure ascertainment. Random effects models were used to estimate pooled effects. RESULTS: Thirty-four studies were included in the analysis. Prepregnancy BMI was positively associated with leukemia risk in offspring (odds ratio [OR] per 5-unit BMI increase =1.07, 95% confidence intervals [CI] = 1.04 to 1.11; I2 = 0.0%). Any maternal diabetes was positively associated with acute lymphoblastic leukemia risk (OR = 1.46, 95% CI = 1.28 to 1.67; I2 = 0.0%), even after restricting to birthweight-adjusted analyses (OR = 1.74, 95% CI = 1.29 to 2.34; I2 = 0.0%), and inversely associated with risk of central nervous system tumors (OR = 0.73, 95% CI = 0.55 to 0.97; I2 = 0.0%). Pregestational diabetes (OR = 1.57, 95% CI = 1.11 to 2.24; I2 = 26.8%) and gestational diabetes (OR = 1.40, 95% CI = 1.12 to 1.75; I2 = 0.0%) were also positively associated with acute lymphoblastic leukemia risk. No statistically significant associations were observed for gestational weight gain. CONCLUSIONS: Maternal obesity and diabetes may be etiologically linked to pediatric cancer, particularly leukemia and central nervous system tumors. Our findings support weight management and glycemic control as important components of maternal and offspring health. Further validation is warranted.

Parental Age and Childhood Lymphoma and Solid Tumor Risk: A Literature Review and Meta-Analysis.

BACKGROUND: Although advanced parental age has been definitively linked to pediatric acute lymphoblastic leukemia, studies of parental age and pediatric solid tumors have not reached firm conclusions. This analysis aimed to elucidate the relationship between parental age and pediatric solid tumors through meta-analysis of existing studies based in population registries. METHODS: We searched Medline (PubMed) and Embase for registry-based studies of parental age and solid tumors through March 2022. We performed random-effects meta-analysis to estimate pooled effects and 95% confidence intervals (CIs). All statistical tests were 2-sided. RESULTS: A total of 15 studies covering 10 childhood solid tumor types (30 323 cases and 3 499 934 controls) were included in this analysis. A 5-year increase in maternal age was associated with an increased risk of combined central nervous system tumors (odds ratio [OR] = 1.07, 95% CI = 1.04 to 1.10), ependymoma (OR = 1.19, 95% CI = 1.09 to 1.31), astrocytoma (OR = 1.10, 95% CI = 1.05 to 1.15), rhabdomyosarcoma (OR = 1.14, 95% CI = 1.03 to 1.25), and germ cell tumors (OR = 1.06, 95% CI = 1.00 to 1.12). A 5-year increase in paternal age was associated with an increased risk of non-Hodgkin lymphoma (OR = 1.06, 95% CI = 1.00 to 1.12). CONCLUSIONS: This meta-analysis of registry-based analyses of parental age and childhood cancer supports the association between older maternal age and certain childhood solid cancers. There is also some evidence that paternal age may be associated with certain cancers such as non-Hodgkin lymphoma. However, as maternal and paternal age are highly correlated, disentangling potential independent causal effects of either factor will require large studies with extensive data on potential confounders.

The Role of Socioeconomic Status and Race/Ethnicity in Malignant Peripheral Nerve Sheath Tumor Survival: A Surveillance, Epidemiology, and End Results-Based Analysis.

BACKGROUND: Recent investigations of malignant peripheral nerve sheath tumor (MPNST) survival have reported higher mortality among non-White individuals. However, previous analyses have not examined the impact of socioeconomic status (SES) on these observations. This study aims to characterize factors associated with cause-specific MPNST survival, including information related to census-tract-level SES (CT-SES). METHODS: We identified 2,432 primary MPNSTs using the Surveillance, Epidemiology, and End Results (SEER) 18 (2000-2016) database. We used Cox proportional hazards modeling to estimate the effects of sex, race/ethnicity, CT-SES quintile, metastasis at diagnosis, tumor site, age at diagnosis, and treatment by surgery on survival. Models were fit in both the full population and, separately, stratified by race/ethnicity and age at diagnosis (<40 vs. ≥40). RESULTS: In adjusted models, age at diagnosis, CT-SES, and metastasis at diagnosis were associated with mortality. In race/ethnicity-stratified analysis, higher CT-SES was found to improve survival only in the White population. Among those diagnosed before age 40, metastasis at diagnosis and American Indian/Alaska Native race/ethnicity were associated with mortality, and both Hispanic ethnicity and Asian/Pacific Islander race were suggestive for increased mortality. Among cases, diagnoses at age 40 and above, age at diagnosis, male sex, and CT-SES were associated with mortality. CONCLUSIONS: This analysis provides evidence that among pediatric and young adult patients, non-White populations experience inferior survival compared with Whites, independent of CT-SES. Our findings also suggest that the effect of CT-SES on MPNST survival may differ by racial/ethnic group. IMPACT: These findings suggest that barriers to healthcare for certain racial/ethnic groups extend beyond SES.

Racial/ethnic and sex differences in young adult malignant brain tumor incidence by histologic type.

BACKGROUND: Brain tumors are among the top four cancers in young adults. We assessed important windows of tumor development and examined the interplay of race/ethnicity, age, and sex in young adult brain tumor incidence. METHODS: Using SEER 18 data (2000-2017), incidence rates were estimated by Poisson regression in individuals aged 20-39 years at diagnosis. Incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated by race/ethnicity, sex and age for 12 malignant histologies. RESULTS: White incidence for all histologies was higher (White vs. Black IRR: 2.09, 95% CI: 1.94, 2.24; White vs Asian Pacific Islander IRR: 1.88, 95% CI: 1.75, 2.03; White vs Hispanic IRR: 1.70, 95% CI: 1.62, 1.78; White vs American Indian IRR: 1.40, 95% CI: 1.14, 1.73). Minority groups had higher lymphoma incidence (White vs Black IRR: 0.32, 95% CI: 0.25, 0.40, White vs Hispanic HR: 0.55, 95% CI: 0.44, 0.68). Males had higher incidence than females for all histologies (IRR: 1.36, 95% CI: 1.31, 1.41). Male rates were highest for lymphoma (male-to-female [MF] IRR: 2.00, 95% CI: 1.65, 2.42) and glioblastoma (MF IRR: 1.61, 95% CI: 1.48, 1.75). The male excess in incidence was similar by race/ethnicity and increased with age (20-24-year-old IRR: 1.18, 95% CI: 1.07, 1.29; 35-39-year-old IRR: 1.44, 95% CI: 1.35, 1.54). CONCLUSIONS: A White race and male incidence excess was observed among brain tumors. IMPACT: The male excess was similar by race/ethnicity and increased with age suggesting male sex may be an intrinsic risk factor for brain tumor development.

Racial and ethnic disparities in pediatric cancer incidence among children and young adults in the United States by single year of age.

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 (2000-2017) 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.