Demographic and socioeconomic characteristics of participants are shown in Table 1. Compared with white parents, non-US–born Hispanic mothers and fathers were younger, more likely to live in urban areas in California, and had fewer years of educational attainment. In comparison with non-US–born Hispanic parents, US-born Hispanic parents were younger and had more years of formal education.

Children of US-born Hispanic mothers had minimally higher rates of low birth weight and early gestational age (Table 2). Hispanic parents were less likely than white parents to have private health insurance or to have multiple-birth pregnancies. Parity was higher among Hispanic parents, particularly when the mother was not born in the United States.

Several cancer types showed differences in risk among all Hispanic children in comparison with white children (Table 3 and eFigure in the Supplement). Acute lymphoblastic leukemia (HR, 1.20; 95% CI, 1.10–1.32 for children of US-born Hispanic mothers; HR, 1.06; 95% CI, 0.98–1.15 for children of non-US–born Hispanic mothers) and Hodgkin lymphoma(HR, 2.49; 95% CI, 1.21–5.13 for children of US-born Hispanic mothers; HR, 2.35; 95% CI, 1.24–4.47 for children of non-US–born Hispanic mothers) were higher among Hispanic children regardless of maternal nativity, while most types of CNS tumors were lower among Hispanic children. Glioma (HR, 0.71; 95% CI, 0.61–0.83 for children of US-born Hispanic mothers; HR, 0.50; 95% CI, 0.44–0.58 for children of non-US–born Hispanic mothers) and neuroblastoma (HR, 0.66; 95% CI, 0.56–0.78 for children of US-born Hispanic mothers; HR, 0.47; 95% CI, 0.40–0.54 for children of non-US–born Hispanic mothers) HRs were lower among all Hispanic children compared with white children. And for both gliomas and neuroblastoma, the HRs were lowest among children of non-US–born Hispanic mothers. The rate of Wilms tumor was lower only among children of non-US–born Hispanic mothers (HR, 0.70; 95% CI, 0.59–0.82). An elevated HR for bone tumors, with wide confidence intervals, was found among children of US-born Hispanic mothers only (HR, 1.38; 95% CI, 0.83–2.31).

When we further restricted the Hispanic category to Mexican individuals, we observed more sharply decreased HRs for non-Hodgkin lymphoma(HR, 0.59; 95% CI, 0.37–0.92), ependymomas( HR, 0.69; 95% CI, 0.49–0.97), and Wilms tumor(HR, 0.69; 95% CI, 0.58–0.82) among the offspring of Mexican born mothers, while yolk sac tumors were found to be increased in children of Mexican mothers (HR, 1.46; 95% CI, 0.99–2.17) (Table 4).

Among the children of non-Mexican US-born Hispanic mothers, we observed an increased risk for unilateral retinoblastoma (HR, 2.03; 95% CI, 1.33–3.11), but otherwise similar patterns of cancer to those seen among Hispanic children as a whole (Table 5).

Although numerous migrant studies have been published in the literature, to our knowledge, few have examined cancer risk among Hispanic immigrants to the United States and no previous study has examined childhood cancer risk among US immigrant populations. Studies in Sweden and the United Kingdom suggested that differences exist in childhood cancer incidence between immigrant and native populations.^8,9 For many cancer types, research on migrant groups has often shown that the initial difference in the incidence of cancer of immigrants changes over 1 or 2 generations to converge to the incidence in the new host population.¹⁷ Similarly, our study suggests that the children of non-US–born Hispanic mothers retain, at least in part, the cancer risk observed in their countries of origin.¹⁸ In this study, we observed notable differences across groups in risk for gliomas and several specific CNS tumor types (high-grade gliomas, low-grade gliomas, ependymoma, astrocytoma, and intracranial and intraspinal embryonal tumors), as well as unilateral retinoblastoma, bone tumors, yolk sac tumors, and neuroblastoma.

As has been reported elsewhere,^5,18 we observed that Hispanic children experience overall higher risk for acute lymphoblastic leukemia and lower risk for CNS tumors, Wilms tumors, and neuroblastoma compared with non-Hispanic white children. There are several hypotheses why Hispanic children may have these differing childhood cancer rates compared with white children, including both genetic variation or differing rates of exposure to infections in early life.^19,20 We also observed excesses of Hodgkin lymphoma among Hispanic children, which may be attributable in part to higher infection rates with Epstein-Barrvirus. Epstein-Barrvirus–positive Hodgkin lymphoma is more common among Hispanic individuals and is associated with mixed cellularity subtype, which we previously observed to be more common among Hispanic children in our sample.²¹

The elevated risks for bone tumors among the children of US-born Hispanic mothers, in comparison with the lower risk among the children of non-US–born Hispanic mothers, was notable given what is known about differences in height between Mexican and Mexican American individuals.²² Height is a risk factor for several adult cancers²³ and has been implicated in some studies of osteosarcoma and Ewing sarcoma.²⁴ Possible mechanisms explaining a mediating effect of height on cancer risk include increases in the number of skeletal cells; growth hormones, such as insulin-like growth factor; or greater energy intake of the child in early life.²⁵

For neuroblastoma, gliomas, and Wilms tumor, we observed a decreased risk with mother’s non-US–born status and intermediate risks among the children of US-born Hispanic mothers. Because little is known about the causes of these cancers,^26–28 our results suggest that it may be fruitful to investigate certain risk factors that differ between Hispanic immigrants by nativity. With regard to birth outcomes, the epidemiologic paradox is thought to be explained by the positive influence of traditional Mexican culture, eg, positive attitudes about pregnancy as well as good care and support of the pregnant woman by her family, which lowers stress; a healthier diet, with low levels of over weight; high uptake of breastfeeding; and extremely low rates of smoking, drinking, or drug use during pregnancy.^11,29 Mexican-born women also have low rates of pregnancy complications.³⁰ In contrast to their non-US–born counterparts, US-born Hispanic women experience more stress during pregnancy; are more likely to have lower-quality diets, higher levels of overweight, and excessive weight gain in pregnancy; are less likely to breastfeed; and are more likely to report any substance use during pregnancy, although not as likely as white women.^11,29,31,32 There are other potentially relevant ways in which the exposures of US-born and non-US–born Hispanic mothers differ, such as residence in over-crowded housing (leading to differing exposure to infectious pathogens), exposure to environmental pollution, occupational exposures, maternal comorbid conditions, the use of prescription medications in pregnancy, or variation in hormone levels.^33–37 Alternatively, the different incidence between Hispanic, white, and mixed-race families may be in part a result of underlying genetic variation. Genetic admixture fractions have previously been shown to be associated with a child’s risk for specific leukemia immunophenotypes.²⁰

For several other cancer types (non-Hodgkin lymphoma, medulloblastoma, and rhabdomyosarcoma), we observed similar risk estimates between US-born and non-US–born Hispanic mothers, suggesting that the behavioral and environmental factors mentioned here play little role in the etiology of these tumors. Little is known on the etiology of yolk sac tumors; however, higher rates of nonseminomas have been previously reported among Hispanic individuals.³⁸

A validation study examining the accuracy of race and ethnicity on California birth certificates found very high sensitivity (99%) in capturing Hispanic ethnicity.³⁹ A source of bias in our study would be whether non-US–born parents returned to their country of origin for the child’s diagnosis and treatment or whether non-US–born parents have greater residential mobility than US-born Hispanic parents. However, one study of California children with leukemia did not find any differences in residential mobility by maternal nativity.¹² Also, the very high rates of childhood cancers among Los Angeles Hispanic children—as noted by Kaatsch,¹⁰ Hispanic children in Los Angeles County have among the highest childhood cancer rates worldwide—would support that most are diagnosed as having cancer while in the United States.

Study limitations included a lack of information on the duration of a mother’s residence in the United States, nor any measures of acculturation, so we were not able to conduct more precise analyses on the effects of immigration on cancer risk. Californiabirthcertificatesdonotcollectthefather’scountryofbirth.

The differing risk observed among children of immigrant and US-born Hispanic mothers was evident for several childhood cancer types. At present, to our knowledge, there are limited studies on the distribution of genotypes related to childhood cancer among Hispanic individuals, and small sample sizes in most childhood cancer studies limit further explorations of genetic variation among ethnic subgroups. Incorporating the immigrant experience into studies of childhood cancer may help to inform research on disease etiology, identify vulnerable populations, and highlight opportunities for cancer prevention. Further studies should explore the differences in risk incurred by variation in environmental, behavioral, and infectious exposures between non-US– and US-born Hispanic mothers.