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Keywords:

  • child;
  • ethnicity;
  • neoplasms/epidemiology;
  • race;
  • risk factors

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

BACKGROUND:

Children of different racial/ethnic backgrounds have varying risks of cancer. However, to the authors' knowledge, few studies to date have examined cancer occurrence in children of mixed ancestry.

METHODS:

This population-based case-control study examined cancer among children aged <15 years using linked cancer and birth registry data from 5 US states from 1978 through 2004. Data were available for 13,249 cancer cases and 36,996 controls selected from birth records. Parental race/ethnicity was determined from birth records. Logistic regression analysis was used to examine the association of cancer with different racial/ethnic groups.

RESULTS:

Compared with whites, blacks had a 28% decreased risk of cancer (odds ratio [OR], 0.72; 95% confidence interval [95% CI], 0.65-0.80), whereas both Asians and Hispanics had an approximate 15% decrease. Children of mixed white/black ancestry also were found to be at decreased risk (OR, 0.71; 95% CI, 0.56-0.90), but estimates for mixed white/Asian and white/Hispanic children did not differ from those of whites. Compared with whites: 1) black and mixed white/black children had decreased ORs for acute lymphoblastic leukemia (OR, 0.39 [95% CI, 0.31-0.49] and OR, 0.58 [95% CI, 0.37-0.91], respectively); 2) Asian and mixed white/Asian children had decreased ORs for brain tumors (OR, 0.51 [95% CI, 0.39-0.68] and OR, 0.79 [95% CI, 0.54-1.16], respectively); and 3) Hispanic and mixed white/Hispanic children had decreased ORs for neuroblastoma (OR, 0.51 [95% CI, 0.42-0.61] and OR, 0.67 [95% CI, 0.50-0.90], respectively).

CONCLUSIONS:

Children of mixed ancestry tend to have disease risks that are more similar to those of racial/ethnic minority children than the white majority group. This tendency may help formulate etiologic studies designed to study possible genetic and environmental differences more directly. Cancer 2010. © 2010 American Cancer Society.

Children of different racial or ethnic backgrounds have varying risks of cancer.1 This observation may be attributable to differences in genetic predisposition as well as environmental exposures. Most studies in the United States have focused on comparisons between children of white and black race,1 although in recent years, studies also have examined cancer rates among Hispanic and Asian children as the sizes of those populations have grown in the United States.2-6 International studies also suggest that rates of different childhood cancers may differ across racial/ethnic groups.7, 8 However, to the best of our knowledge, very few studies to date have specifically examined cancer occurrence in mixed ancestry children9, 10 because the proportion of mixed ancestry individuals is typically low in most countries (eg, <3% in the United States).11 Examination of mixed race/ethnicity children may provide added insight into possible genetic and environmental factors associated with oncogenesis.

The current analysis used cancer registry data from 5 states that comprise approximately 30% of the United States pediatric population.11 The large study size and the inclusion of several racially and ethnically diverse states allowed examination of common childhood cancers across racial/ethnic groups and, in particular, among children of mixed race/ethnicity. In addition to providing race/ethnicity information regarding children's parents (information unavailable in cancer registries), the use of birth records to obtain subject data also permitted adjustment of several birth factors that could potentially mediate differences in cancer risk.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Study Population

Human subject protection committee approval was received by the participating institutions before the study was conducted. Five states (California, Minnesota, New York [excluding New York City], Texas, and Washington) have previously linked birth records to their state cancer registries for selected years ranging from 1970 to 2004. Cases were classified using the International Classification of Childhood Cancer12 from the original International Classification of Diseases for Oncology codes (version 2 or 3, depending on state). For this analysis, Burkitt lymphoma was analyzed as part of non-Hodgkin lymphoma. A separate “embryonal” tumor group also was created comprised of embryonal central nervous system (CNS) tumors, neuroblastomas, retinoblastomas, Wilms tumors, hepatoblastomas, and embryonal rhabdomyosarcomas.

Each state also selected controls from birth records matched to cases on the basis of birth year (all states) and sex (California and Texas only). Variable control:case matching ratios were used, ranging from 1:1 in Texas to 10:1 in Washington. Details of each state's linkages have been described previously.13-17 For this analysis, these state datasets were pooled with the following modifications: cancer diagnoses were restricted to those aged 28 days through 14 years (through 4 years in California), subjects who were selected as controls were excluded from the pooled control group (allowed in Minnesota and New York), and subjects with Down syndrome were excluded (data unavailable in Texas before 1984 and Washington before 1989). Last, analysis was restricted to years for which parental race/ethnicity was recorded in birth records and available for both parents: 1983 through 1997 in California, 1989 through 2004 in Minnesota, 1978 through 2001 in New York, 1980 through 1998 in Texas, and 1988 through 2004 in Washington. During this time period, 1948 (12.8%) and 6254 (14.3%) otherwise eligible cases and controls, respectively, had race/ethnicity information for 1 or both parents missing. The final dataset included 13,249 cases of childhood cancer and 36,996 controls.

Variable Specification

The primary variable of interest was parental race and ethnicity. Separate child's race/ethnicity was not available from all states. Parental racial groups were recorded on birth records with varying categorizations by state and time period; for the current analysis, they were summarily categorized as: white, black, Asian, Native American, and Other. Pacific Islanders were grouped with Asians in the pooled dataset. Ethnicity was classified as Hispanic versus non-Hispanic on birth records. For this analysis, a combined race/ethnicity categorization was created comprised of Hispanics (regardless of race) and all racial groups exclusive of Hispanics. Children were classified into discrete categories based on their parents' ancestry, including mixed ancestry offspring (Table 1). Given the large number of possible mixed ancestry combinations and relatively small numbers, we decided a priori to analyze only selected groups of mixed white ancestry children.

Table 1. Distribution of Cases and Controls According to Parental Ancestry
Cancer TypeaParental Ancestry, No. (%)Total
White/ WhiteWhite/ BlackBlack/ BlackWhite/ HispanicHispanic/ HispanicWhite/ AsianAsian/ AsianNative/ NativeOther/ OtherOther/ Mixed
  • a

    Based on International Classification of Childhood Cancer.12 Subtypes may not sum because only more common cancer subtypes are shown.

  • b

    Cases overlap with those in other categories, because it includes embryonal central nervous system tumors and embryonal rhabdomyosarcomas.

Controls24,526 (66.3)464 (1.3)1719 (4.6)1607 (4.3)5686 (15.4)635 (1.7)1438 (3.9)149 (0.4)30 (0.1)742 (2.0)36,996
All cancers8332 (62.9)98 (0.7)634 (4.8)653 (4.9)2686 (20.3)159 (1.2)456 (3.4)24 (0.2)14 (0.1)193 (1.5)13,249
Leukemia2731 (59.0)31 (0.7)140 (3.0)258 (5.6)1128 (24.4)65 (1.4)192 (4.1)14 (0.3)5 (0.1)67 (1.4)4631
 Acute lymphoblastic2242 (59.7)21 (0.6)96 (2.6)196 (5.2)931 (24.8)51 (1.4)145 (3.9)12 (0.3)4 (0.1)55 (1.5)3753
 Acute myeloid360 (55.5)8 (1.2)38 (5.9)43 (6.6)145 (22.3)10 (1.5)33 (5.1)2 (0.3)0 (0.0)10 (1.5)649
Lymphoma660 (66.4)7 (0.7)49 (4.9)41 (4.1)186 (18.7)6 (0.6)28 (2.8)1 (0.1)3 (0.3)13 (1.3)994
 Hodgkin168 (63.4)1 (0.4)17 (6.4)16 (6.0)61 (23.0)0 (0.0)1 (0.4)0 (0.0)0 (0.0)1 (0.4)265
 Non-Hodgkin409 (69.9)4 (0.7)30 (5.1)17 (2.9)86 (14.7)4 (0.7)21 (3.6)0 (0.0)3 (0.5)11 (1.9)585
Central nervous system1900 (68.2)21 (0.8)157 (5.6)129 (4.6)453 (16.3)29 (1.0)60 (2.2)3 (0.1)2 (0.1)33 (1.2)2787
 Ependymoma198 (65.1)0 (0.0)18 (5.9)12 (3.9)54 (17.8)7 (2.3)10 (3.3)0 (0.0)1 (0.3)4 (1.3)304
 Astrocytoma860 (72.5)9 (0.8)68 (5.7)53 (4.5)149 (12.6)13 (1.1)25 (2.1)1 (0.1)0 (0.0)8 (0.7)1186
 Intracranial embryonal447 (64.2)6 (0.9)27 (3.9)40 (5.7)145 (20.8)7 (1.0)10 (1.4)2 (0.3)1 (0.1)11 (1.6)696
 Other glioma243 (68.8)5 (1.4)24 (6.8)12 (3.4)54 (15.3)1 (0.3)9 (2.5)0 (0.0)0 (0.0)5 (1.4)353
Embryonalb2453 (62.4)36 (0.9)233 (5.9)201 (5.1)757 (19.3)51 (1.3)122 (3.1)7 (0.2)3 (0.1)69 (1.8)3932
 Neuroblastoma806 (67.3)9 (0.8)65 (5.4)53 (4.4)186 (15.5)17 (1.4)36 (3.0)2 (0.2)1 (0.1)22 (1.8)1197
 Retinoblastoma267 (46.8)5 (0.9)45 (7.9)42 (7.4)162 (28.4)10 (1.8)30 (5.3)1 (0.2)0 (0.0)8 (1.4)570
 Wilms tumor617 (63.8)9 (0.9)78 (8.1)48 (5.0)162 (16.8)11 (1.1)20 (2.1)1 (0.1)1 (0.1)20 (2.1)967
 Hepatoblastoma124 (56.4)4 (1.8)5 (2.3)9 (4.1)61 (27.7)1 (0.5)14 (6.4)0 (0.0)0 (0.0)2 (0.9)220
Soft tissue sarcoma519 (66.6)7 (0.9)45 (5.8)28 (3.6)129 (16.6)9 (1.2)31 (4.0)1 (0.1)0 (0.0)10 (1.3)779
 Rhabdomyosarcoma300 (67.1)5 (1.1)25 (5.6)17 (3.8)66 (14.8)7 (1.6)19 (4.3)1 (0.200 (0.0)7 (1.6)447
Bone258 (72.3)2 (0.6)14 (3.9)10 (2.8)63 (17.6)1 (0.3)6 (1.7)1 (0.3)0 (0.0)2 (0.6)357
 Osteosarcoma108 (65.9)1 (0.6)11 (6.7)5 (3.0)34 (20.7)1 (0.6)2 (1.2)1 (0.6)0 (0.0)1 (0.6)164
 Ewing sarcoma120 (78.4)1 (0.7)2 (1.3)4 (2.6)22 (14.4)0 (0.0)3 (2.0)0 (0.0)0 (0.0)1 (0.7)153
Germ cell210 (51.6)0 (0.0)15 (3.7)24 (5.9)108 (26.5)7 (1.7)33 (8.1)0 (0.0)1 (0.2)9 (2.2)407
 Extracranial64 (59.3)0 (0.0)4 (3.7)5 (4.6)18 (16.7)4 (3.7)11 (10.2)0 (0.0)0 (0.0)2 (1.9)108
 Gonadal82 (41.2)0 (0.0)7 (3.5)14 (7.0)69 (34.7)2 (1.0)19 (9.5)0 (0.0)0 (0.0)6 (3.0)199

Other variables used in this analysis were as follows: maternal age (<25 years, 25-29 years, 30-34 years, and ≥35 years), maternal education (<12 years, 12 years, 13-16 years, and ≥17 years), birth year, offspring sex, gestational age (<37 weeks, 37-41 weeks, and ≥42 weeks, preferentially based on last menstrual period), birth weight (<2500 g, 2500-3999 g, ≥4000 g), plurality (singleton, multiple birth), and birth order (first, second, or higher). Gestation <20 weeks or ≥45 weeks and birth weights <350 g were considered implausible and treated as missing.

Statistical Analyses

Cancer risk associated with each race/ethnicity category was estimated using odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression (SAS version 9.1; SAS Institute Inc, Cary, NC). Individual matching in the California dataset was broken for this reason; frequency matching was used by the other states. ORs were estimated only for those strata with at least 3 observations. All estimates were adjusted by state, maternal age, birth year, offspring sex, gestational age, birth weight, plurality, and birth order. Because 26% of our study population did not have maternal education information recorded, maternal education was not included in the final model. However, sensitivity analyses that included maternal education demonstrated no substantial differences from our main results (data not shown). Given the different control:case ratios for each state, a separate sensitivity analysis with only 1 randomly selected control per case was conducted, which also indicated no differences from our reported results (data not shown). Additional analyses examined differences between racial/ethnic associations stratified by age and possible statistical interactions between racial/ethnic groups and offspring sex.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Same-race white children comprised 62.9% of cases and 66.3% of controls (Table 1). Same-race Hispanic children formed the second largest racial/ethnic group, comprising 20.3% of cases and 15.4% of controls, and mixed ancestry children accounted for 8.3% of cases and 9.3% of controls. Compared with the study population, the distribution of cancer diagnoses among children with incomplete parental ancestry was similar (data not shown). However, compared with the study population (Table 2), offspring with missing ancestry were more likely to have mothers who were younger (aged <25 years: 54.3% vs 32.3%) and less education (<12 years: 33.6% vs 18.1%), and were themselves more likely to be first born (50.3% vs 39.6%), born prematurely (<37 weeks: 12.0% vs 8.0%), and with lower birth weight (<2500 g: 8.8% vs 5.2%). The distribution of other demographic and perinatal characteristics among those with missing parental ancestry information did not differ between cases and controls (data not shown).

Table 2. Characteristics of Cases and Controls
CharacteristicCases, n = 13,249 No. (%)Controls, n = 36,996 No. (%)
  • a

    Available only for selected years (Minnesota and New York, all years; California and Texas, 1989-onward; and Washington, 1992-onward).

State of birth
 California4064 (30.7)8437 (22.8)
 Minnesota1033 (7.8)4071 (11.0)
 New York3195 (24.1)7676 (20.7)
 Texas3666 (27.7)3697 (10.0)
 Washington1291 (9.7)13,115 (35.4)
Maternal age, y
 <254193 (31.7)12,032 (32.5)
 25-294364 (32.9)11,983 (32.4)
 30-343194 (24.1)8827 (23.9)
 ≥351496 (11.3)4142 (11.2)
 Missing212
Maternal education, ya 
 <121842 (19.2)4852 (17.7)
 123231 (33.7)9244 (33.8)
 13-163597 (37.5)10,706 (39.2)
 ≥17916 (9.6)2537 (9.3)
 Missing206914
Birth y
 1978-19852461 (18.6)5024 (13.6)
 1986-19893643 (27.5)8157 (22.0)
 1990-19934229 (31.9)11,843 (32.0)
 1994-20042916 (22.0)11,972 (32.4)
Offspring sex
 Male7335 (55.4)19,676 (53.2)
 Female5914 (44.6)17,319 (46.8)
 Missing01
Gestational age, wk
 <371102 (8.6)2813 (7.8)
 37-4110,041 (78.0)28,367 (78.5)
 ≥421732 (13.4)4938 (13.7)
 Missing374878
Birth weight, g
 <2500720 (5.4)1871 (5.1)
 2500-399910,660 (80.5)30,253 (81.9)
 ≥40001855 (14.0)4815 (13.0)
 Missing1457
Birth order
 15274 (40.0)14,503 (39.4)
 24454 (33.8)12,303 (33.4)
 ≥33462 (26.2)9998 (27.2)
 Missing59192

Overall Cancer Risk

When the overall risk of cancer was examined across unmixed racial/ethnic groups, black, Asian, and Hispanic children were found to have significantly decreased ORs for cancer compared with children of white ancestry (Table 3) (Fig. 1A). Black children had the largest decrease (OR, 0.72; 95% CI, 0.65-0.80) followed by Asian and Hispanic children, both with approximately 15% relative decreases. Compared with white children, those of mixed white/black ancestry had a similar risk as black children (OR, 0.71; 95% CI, 0.56-0.90), but estimates for white/Asian and white/Hispanic children were no longer significantly decreased (OR, 0.91 for both groups).

thumbnail image

Figure 1. (A-D): Odds ratios and 95% confidence intervals for selected diagnostic groups stratified by parental ancestry are shown. Adjustment variables are listed in Table 2 (except maternal education). Risk estimates for Native/Native (N/N) and Other/Other (O/O) were combined if neither group had ≥3 observations. WW indicates White/White (referent group); WB, White/Black; BB, Black/Black; WH, White/Hispanic; HH, Hispanic/Hispanic; WA, White/Asian; AA, Asian/Asian.

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Table 3. Cancer Risk Stratified by Parental Ancestry: Adjusted by Birth Year, State, Maternal Age, Plurality, Birth Order, Child's Sex, Gestational Age, and Birth Weighta
Cancer TypeOdds Ratio (95% CI)
White/ WhiteWhite/ BlackBlack/ BlackWhite/ HispanicHispanic/ HispanicWhite/ AsianAsian/ AsianNative/ NativeOther/ OtherOther/ Mixed
  • a

    Risk estimates were not calculated for groups with <3 observations. Native/Native was combined with Other/Other if combined group had ≥3 observations. If Native/Native combined with Other/Other still had <3 observations, then both groups also were combined with Other/Mixed.

All cancersReferent0.71 (0.56-0.90)0.72 (0.65-0.80)0.91 (0.82-1.01)0.86 (0.81-0.91)0.91 (0.75-1.10)0.85 (0.75-0.95)0.89 (0.56-1.42)0.70 (0.36-1.36)0.83 (0.70-0.99)
LeukemiaReferent0.70 (0.48-1.03)0.47 (0.39-0.57)1.06 (0.92-1.23)1.07 (0.98-1.17)1.01 (0.76-1.35)0.99 (0.84-1.18)1.56 (0.85-2.87)0.79 (0.30-2.10)0.88 (0.67-1.16)
 Acute lymphoblasticReferent0.58 (0.37-0.91)0.39 (0.31-0.49)0.98 (0.83-1.16)1.06 (0.96-1.17)0.95 (0.69-1.30)0.91 (0.76-1.10)1.63 (0.84-3.15)0.78 (0.27-2.28)0.85 (0.63-1.15)
 Acute myeloidReferent1.39 (0.68-2.85)0.98 (0.69-1.40)1.31 (0.93-1.86)1.08 (0.86-1.36)1.22 (0.62-2.39)1.29 (0.87-1.91)1.07 (0.60-1.92)
LymphomaReferent0.88 (0.41-1.88)0.80 (0.59-1.10)0.97 (0.70-1.36)1.10 (0.90-1.34)0.70 (0.31-1.59)1.14 (0.76-1.70)1.00 (0.36-2.77)0.95 (0.51-1.74)
 HodgkinReferent1.05 (0.60-1.84)1.84 (1.07-3.15)1.94 (1.36-2.77)0.29 (0.09-0.93)
 Non-HodgkinReferent0.76 (0.28-2.04)0.82 (0.56-1.20)0.59 (0.36-0.99)0.73 (0.55-0.95)0.67 (0.25-1.83)1.14 (0.71-1.82)1.34 (0.42-4.30)1.11 (0.57-2.18)
Central nervous systemReferent0.67 (0.42-1.05)0.76 (0.63-0.91)0.79 (0.65-0.96)0.66 (0.58-0.74)0.79 (0.54-1.16)0.51 (0.39-0.68)0.48 (0.19-1.18)0.67 (0.47-0.97)
 EpendymomaReferent0.83 (0.50-1.38)0.61 (0.33-1.14)0.66 (0.47-0.93)1.73 (0.80-3.75)0.74 (0.37-1.47)0.40 (0.15-1.09)
 AstrocytomaReferent0.70 (0.36-1.37)0.75 (0.57-0.98)0.77 (0.57-1.03)0.52 (0.43-0.64)0.81 (0.46-1.42)0.50 (0.33-0.76)0.37 (0.19-0.71)
 Intracranial embryonalReferent0.78 (0.34-1.76)0.53 (0.35-0.79)0.96 (0.68-1.35)0.78 (0.63-0.97)0.74 (0.34-1.57)0.31 (0.16-0.60)1.34 (0.42-4.25)0.84 (0.46-1.55)
 Other gliomaReferent1.42 (0.58-3.48)0.95 (0.61-1.47)0.63 (0.35-1.14)0.68 (0.49-0.95)0.58 (0.27-1.25)0.52 (0.23-1.17)
EmbryonalReferent0.79 (0.56-1.13)0.87 (0.75-1.02)0.84 (0.72-0.99)0.73 (0.66-0.81)0.85 (0.63-1.15)0.62 (0.51-0.76)0.94 (0.44-2.04)0.66 (0.20-2.19)0.84 (0.64-1.10)
 NeuroblastomaReferent0.57 (0.29-1.11)0.74 (0.56-0.96)0.67 (0.50-0.90)0.51 (0.42-0.61)0.82 (0.50-1.35)0.52 (0.36-0.74)0.78 (0.25-2.46)0.70 (0.44-1.13)
 RetinoblastomaReferent0.90 (0.37-2.20)1.34 (0.96-1.88)1.39 (0.97-1.98)1.17 (0.93-1.47)1.37 (0.72-2.62)1.26 (0.85-1.87)0.69 (0.34-1.41)
 WilmsReferent0.85 (0.44-1.67)1.26 (0.98-1.63)0.82 (0.60-1.13)0.69 (0.56-0.84)0.75 (0.41-1.39)0.39 (0.24-0.63)1.06 (0.68-1.66)
 HepatoblastomaReferent1.68 (0.61-4.61)0.29 (0.11-0.80)0.83 (0.41-1.66)1.31 (0.90-1.90)1.48 (0.83-2.64)0.26 (0.07-1.08)
Soft tissue sarcomaReferent0.90 (0.42-1.92)0.86 (0.62-1.19)0.67 (0.45-1.00)0.74 (0.59-0.92)0.92 (0.47-1.81)1.01 (0.68-1.49)0.67 (0.35-1.26)
 RhabdomyosarcomaReferent1.10 (0.45-2.69)0.86 (0.56-1.32)0.67 (0.40-1.12)0.65 (0.48-0.88)1.13 (0.53-2.43)0.91 (0.55-1.51)0.93 (0.46-1.90)
BoneReferent0.63 (0.36-1.10)0.68 (0.36-1.31)1.10 (0.80-1.52)0.96 (0.42-2.20)0.56 (0.25-1.28)
 OsteosarcomaReferent1.29 (0.67-2.42)0.89 (0.36-2.23)1.65 (1.05-2.69)1.02 (0.44-2.36)
 Ewing sarcomaReferent0.57 (0.21-1.57)0.77 (0.46-1.29)0.85 (0.27-2.76)0.25 (0.09-0.68)
Germ cellReferent0.68 (0.40-1.15)1.36 (0.88-2.11)1.33 (1.01-1.75)1.78 (0.82-3.84)2.63 (1.78-3.90)0.90 (0.46-1.77)
 ExtracranialReferent0.54 (0.19-1.51)0.75 (0.30-1.90)0.53 (0.29-0.94)2.19 (0.78-6.20)1.84 (0.94-3.63)0.23 (0.03-1.70)
 GonadalReferent0.80 (0.36-1.75)2.08 (1.16-3.76)2.21 (1.50-3.27)4.00 (2.34-6.83)1.50 (0.71-3.13)

Hematologic Cancers

Black children also had the lowest OR for acute lymphoblastic leukemia (ALL) versus white children (OR, 0.39; 95% CI, 0.31-0.49) (Table 3) (Fig. 1B), with mixed white/black children at intermediate risk (OR, 0.58 [95% CI, 0.37-0.91] vs white children; OR, 1.49 [95% CI 0.91-2.44] vs black children). Native American children had the greatest risk of ALL compared with white children (OR, 1.63; 95% CI, 0.84-3.15). Among lymphomas, only Hispanic and mixed white/Hispanic children had increased ORs (1.94 and 1.84, respectively) for Hodgkin lymphoma compared with white children. In contrast, compared with white ancestry, being Hispanic or white/Hispanic was associated with a borderline decreased risk of developing non-Hodgkin lymphoma (ORs, 0.73 and 0.59, respectively).

CNS Tumors

Compared with whites, most non-white groups had decreased ORs for CNS tumors (Table 3) (Fig. 1C), with Asian children having the lowest risk (OR, 0.51; 95% CI, 0.39-0.68), followed by Hispanic and black children. Children of mixed white/Asian ancestry were at intermediate risk (OR, 0.79 [95% CI, 0.54-1.16] vs white children; OR, 1.56 [95% CI, 0.97-2.50] vs Asian children). Risk estimates for mixed white/black and white/Hispanic children were similar to same-race black and Hispanic children, respectively. This pattern of decreased ORs among non-white groups also was observed across most individual CNS tumor histologies, although estimates often lacked precision.

Embryonal Tumors

Among embryonal tumors, there were wide differences in the ORs for neuroblastoma, with black, Asian, and Hispanic children at progressively decreased risk versus the white referent group (Hispanic children: OR, 0.51; 95% CI, 0.42-0.61) (Table 3) (Fig. 1D). Neuroblastoma risk estimates for mixed-race/ethnicity groups compared with white children were imprecise except for mixed white/Hispanic children (OR, 0.67; 95% CI, 0.50-0.90). Estimates for retinoblastoma were similarly imprecise for most groups, with black and mixed white/Hispanic race associated with borderline increased ORs (1.34 and 1.39, respectively) versus white race. Hispanic and particularly Asian ancestry (OR, 0.39; 95% CI, 0.24-0.63) were associated with a decreased risk of Wilms tumor, whereas black children were at borderline increased risk. Mixed ancestry groups generally had imprecise estimates. Only black children were found to be at a significantly different risk of hepatoblastoma compared with white children (OR, 0.29 [95% CI, 0.11-0.80]; black vs mixed white/black children: OR, 0.17 [95% CI, 0.04-0.71]).

Sarcomas

Only Hispanic children were found to have a significantly decreased OR for soft tissue sarcomas versus white children (OR, 0.74; 95% CI, 0.59-0.92) (Table 3). In contrast, Hispanic children had an increased risk of osteosarcoma (OR, 1.65; 95% CI, 1.05-2.69). Only 2 black and 1 mixed white/black individuals were diagnosed with Ewing sarcoma in our population (combined OR, 0.25; 95% CI, 0.08-0.79). Most sarcoma histologies had insufficient sample size to allow estimation for mixed ancestry groups.

Germ Cell Tumors

Both Hispanic and Asian children had significantly increased ORs for germ cell tumors compared with white children (ORs, 1.33 [95% CI, 1.01-1.75] and 2.63 [95% CI, 1.78-3.90], respectively) (Table 3). This risk appeared to be primarily due to increased risk of gonadal tumors rather than other extracranial lesions. Hispanic ancestry was associated with a decreased risk of extracranial nongonadal germ cell tumors versus white ancestry (OR, 0.53; 95% CI, 0.29-0.94). In general, estimates for mixed white/Hispanic and white/Asian individuals appeared similar to same-race Hispanic and Asian estimates, respectively.

Effect of Age at Diagnosis and Offspring Sex

Most racial/ethnic groups demonstrated little difference in overall cancer risk when those diagnosed at age <5 years were compared with those diagnosed at age ≥5 years. The risk of cancer among Hispanic (but not white/Hispanics) compared with white children was lower among the younger group (aged <5 years: OR, 0.82 [95% CI, 0.76-0.88]; aged ≥5 years: OR, 1.00 [95% CI, 0.89-1.13]). Among Native Americans, the opposite pattern was noted, although estimates were imprecise (aged <5 years: OR, 1.05 [95% CI, 0.63-1.78]; aged ≥5 years: OR, 0.56 [95% CI, 0.22-1.39]). When ALL was examined separately, Hispanic ancestry demonstrated the greatest discrepancy compared with white ancestry (aged <5 years: OR, 0.99 [95% CI, 0.89-1.11]; aged ≥5 years: OR, 1.38 [95% CI, 1.12-1.69]). Among children with lymphoma, Asians had the greatest discrepancy compared with whites (aged <5 years: OR, 1.61 [95% CI, 1.03-2.51]; aged ≥5 years: OR, 0.73 [95% CI, 0.48-1.10]). Racial/ethnic groups had similar risk estimates for CNS tumors across age groups (data not shown). ORs for neuroblastoma and Wilms tumor were examined among those diagnosed at age <2 years versus ≥2 years. Although no differences were observed for Wilms tumor, Asian and mixed white/Asian children were found to have lower risks of neuroblastoma compared with whites, particularly among those diagnosed at age <2 years (OR, 0.34 [95% CI, 0.20-0.58] and 0.66 [95% CI, 0.34-1.30], respectively) versus those diagnosed at age ≥2 years (OR, 0.85 [95% CI, 0.53-1.37] and 1.12 [95% CI, 0.55-2.30]), respectively.

When statistical interaction between race/ethnicity and offspring sex was explored among the more common cancer subtypes, only neuroblastoma demonstrated a possible interaction (overall P = .04). The decreased risk of neuroblastoma associated with black ancestry compared with white ancestry was noted primarily among females (OR, 0.41 [95% CI, 0.25-0.67] vs males: OR, 1.03 [95% CI, 0.75-1.42]). A similar pattern of relatively decreased risk also was observed among female mixed white/black children, but estimates were imprecise. Risk estimates for other ancestry groups were similar across sex.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

In our pooled analysis, we observed significant variability in childhood cancer risk across different racial/ethnic groups. The size and diversity of our population catchment area is similar to that surveyed by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, except we had fewer Native Americans but a larger number of Hispanics.11, 18 Similar to our findings, SEER data suggest that compared with whites, black children have a decreased risk of cancer overall, and particularly of ALL, Ewing sarcoma, and germ cell tumors.1 More modest decreased risks of CNS tumors and neuroblastoma also were observed. We did not find black children to be at a decreased risk for Hodgkin lymphoma or at an increased risk of soft tissue sarcomas, as reported by SEER. However, this discrepancy may be due to our study population being limited to those diagnosed at age <15 years; racial differences for these tumor types were greatest among older teens.1 Differences between our results and those using cancer registry data alone also may be due to our ability to adjust for several birth factors potentially related to both race/ethnicity and risk of childhood cancer.

To our knowledge, few studies to date have examined the cancer risk among children of mixed ancestry. South African studies suggest that children of European ancestry had incidence rates of ALL similar to those of white children in the United States, but rates among South African black children were >50% lower.9, 10 Mixed race children in South Africa had intermediate rates of ALL.9, 10 In the current study, mixed white/black children had a decreased overall risk of cancer similar to that for black children, although estimates for ALL may be intermediate between those of same-race black and white children.

Data from the current study and others suggest that Hispanic children have a decreased risk of cancer overall versus non-Hispanic whites.1, 3 In the current study, compared with non-Hispanic whites, Hispanics had an increased risk of Hodgkin lymphoma, osteosarcoma, and gonadal germ cell tumor, but a decreased risk of non-Hodgkin lymphoma, extracranial germ cell tumor, CNS tumor, neuroblastoma, Wilms tumor, and soft tissue sarcoma. Data from Florida suggest that Hispanics residing there, who are primarily of Cuban and Central American ancestry as opposed to the predominantly Mexican ancestry Hispanics living in California and Texas, had a significantly higher rate of non-Hodgkin lymphoma.4 In contrast to the Florida study,4 we also did not find Hispanics to be at an increased risk of developing ALL overall. Similar to results from a prior California study3 with which we shared overlapping cases, we did not find Hispanic children aged <5 years to be at a significantly increased risk of ALL. However, although our study did not include California children diagnosed at ≥5 years of age, similar to that study3 our data from other states suggest that the risk of ALL may be increased among older Hispanic children versus non-Hispanic white children. Our use of birth records also restricts cases to those born in the United States, and it is possible that relevant prenatal and postnatal exposures may differ between foreign-born and native-born Hispanics. Lastly, our risk estimates for mixed white/Hispanic children either were similar to Hispanics or intermediate between Hispanic and white same-race/ethnicity groups. We are unaware of prior studies examining this mixed ancestry group specifically.

Compared with white children, we found that Asian children had a decreased risk of cancer overall, and specifically of CNS tumors, neuroblastoma, and Wilms tumor, but an increased risk of germ cell tumor. A California study also reported decreased incidence rates of CNS and Wilms tumors and an increased rate of germ cell tumors among Asians.5 Although the number of Asians diagnosed with lymphoma was small in our study, Asians may have lower incidence rates of Hodgkin lymphoma but higher rates of non-Hodgkin lymphoma compared with whites.5 An increased risk of both Hodgkin and non-Hodgkin lymphomas also was observed among South Asians living in Great Britain.8 In the current study, risk estimates for mixed white/Asian children were for the most part intermediate between white and Asian same-race estimates.

The number of Native Americans in the current study was limited. Data from SEER, New Mexico, and Alaska suggest that Native Americans have lower rates of cancer versus whites.1, 19 However, those of Eskimo/Aleutian ancestry may have cancer rates that are more similar to whites than other Native Americans.20

Overall, although our study included nearly 5000 children of racial/ethnic minorities, our power to detect significant differences among less common cancer types and racial/ethnic groups was limited. It is possible some associations we reported may be due to chance. Furthermore, because of limited sample size and differences with regard to how detailed racial/ethnic data from individual states were, certain groups such as Asians and Pacific Islanders were combined, masking potential heterogeneity. Nevertheless, for overall cancer risk and the more common cancer types, the statistical power associated with this study was robust, as demonstrated by analysis of confidence limits.21

Race/ethnicity is a surrogate measure of underlying genetic as well as environmental exposures, neither of which we could measure directly except by maternal and perinatal characteristics as recorded on birth certificates. We adjusted for maternal age and birth weight, both of which have been associated with differential risk of some childhood cancers.22, 23 Studies with access to genetic material have shown that differences may exist in both tumor as well as germline DNA across racial/ethnic groups. For example, Hispanic and white children may have different ALL cytogenetic profiles24 which may partially account for racial/ethnic differences in survival.25 The distribution of germline polymorphisms also differs across racial/ethnic groups, potentially making certain groups more susceptible to certain cancers.26 However, with the exception of rare inherited tumor predisposition syndromes, the magnitude of most genetic associations identified to date has been modest.1, 27 Similarly, to the best of our knowledge, few consistent environmental risk factors have been identified for childhood cancers, and most also have been associated with only modestly increased risk.1, 28 However, it remains plausible that different racial/ethnic groups may have variable levels of environmental exposures, and that there may be important interactions between selected exposures and one's underlying genetic susceptibility.

The current study also was limited by the methods used to identify race/ethnicity, which may vary between and within states.29, 30 Race/ethnicity may be self-reported by parents, abstracted from the medical chart, or, in some instances, recorded by hospital staff based on their own observations.29 However, in validation studies in which birth certificate data were compared with structured postpartum interviews, the sensitivity of birth records to correctly identify most racial/ethnic groups was >94% with the exception of Native Americans.29 Therefore, race information collected on birth records remains widely used in health research.31 Although there may be some misclassification, there is no reason to suspect that, within any racial/ethnic group, parents of children who go on to develop cancer would have their race/ethnicity recorded differently than controls. Our use of same-state controls and adjustment by state and birth year should minimize possible biases introduced by differences in racial/ethnicity classification across states and over time.

Although cancer and birth registries typically record a child's race/ethnicity, our use of parental race/ethnicity to define the child's race/ethnicity has some advantages. Compared with single-race/ethnicity individuals, the racial/ethnic identification of multiracial individuals tends to be less consistent over time, even in studies based on individual self-report.32 More importantly, since 1989, race and ethnicity assigned to infants on birth certificates has often automatically been that of the mother,29 which would preclude using child's race/ethnicity to identify mixed ancestry individuals.

In summary, we found significant variability in childhood cancer risk across racial/ethnic groups. Lacking a better understanding of the genetic and environmental factors that predispose toward cancer, the identification of race/ethnicity, however imprecise, remains an important characteristic in describing cancer risk. The tendency of mixed ancestry children to have risks more similar to those of racial/ethnic minority children than the white majority group in this study may help formulate etiologic studies designed to more directly study those genetic and environmental differences.

CONFLICT OF INTEREST DISCLOSURES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES

Supported by the Children's Cancer Research Fund, Minneapolis, Minnesota; the National Cancer Institute (T32 CA099936 to Minnesota, N01-CN-05,230 to Washington, R01CA717450 to California, and R01CA92670 to Texas); the Fred Hutchinson Cancer Research Center; the Centers for Disease Control and Prevention's National Program of Cancer Registries by cooperative agreement (U58DP000783-01 to New York); and the Leukemia and Lymphoma Society Special Fellowship in Clinical Research (4447-09 to E.J.C.).

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. CONFLICT OF INTEREST DISCLOSURES
  7. REFERENCES