. 2022 Jan 27;8(3):354–363. doi: 10.1001/jamaoncol.2021.6826

Table 2. Association of Genetic Ancestries (25% Interval) as Continuous Variables With Biological Subtypes.

Subtype	Overall P value^a	Percentage African		Percentage Native American^b		Percentage East Asian^b		Percentage South Asian^b
Subtype	Overall P value^a	OR (95% CI)^c	P value^a	OR (95% CI)	P value^a	OR (95% CI)^c	P value^a	OR (95% CI)^c	P value^a
B-ALL
Hyperdiploid	<.001^d	0.77 (0.68-0.86)	<.001^d	0.86 (0.78-0.94)	<.001^d	0.95 (0.88-1.02)	.20	0.84 (0.70-0.98)	.02
ETV6-RUNX1	.001^d	1.07 (0.96-1.20)	.22	0.80 (0.70-0.91)	<.001^d	0.98 (0.89-1.06)	.59	1.10 (0.94-1.27)	.24
B other	<.001^d	0.94 (0.78-1.10)	.45	1.32 (1.18-1.47)	<.001^d	0.96 (0.85-1.08)	.51	0.88 (0.64-1.11)	.30
BCR-ABL1–like	<.001^d	0.84 (0.68-1.02)	.08	1.12 (0.98-1.26)	.10	0.79 (0.66-0.92)	.002^d	0.81 (0.55-1.07)	.16
PAX5alt	.09	1.15 (0.97-1.35)	.11	1.10 (0.93-1.27)	.26	1.15 (1.02-1.30)	.02	1.19 (0.94-1.45)	.14
DUX4	<.001^d	0.70 (0.48-0.93)	.01^d	1.02 (0.85-1.2)	.83	1.30 (1.16-1.45)	<.001^d	1.26 (1.01-1.52)	.04
CRLF2	<.001^d	0.78 (0.54-1.04)	.09	1.48 (1.29-1.69)	<.001^d	0.81 (0.64-0.99)	.04	1.18 (0.88-1.49)	.25
TCF3-PBX1	<.001^d	1.49 (1.25-1.76)	<.001^d	1.30 (1.09-1.53)	.004^d	1.19 (1.01-1.38)	.03	1.02 (0.67-1.38)	.91
KMT2A	.47	1.09 (0.85-1.36)	.47	0.86 (0.64-1.10)	.25	0.94 (0.76-1.13)	.52	1.18 (0.85-1.52)	.29
BCR-ABL1	.79	0.96 (0.71-1.24)	.79	0.89 (0.66-1.13)	.34	1.03 (0.84-1.22)	.79	0.92 (0.54-1.30)	.69
ETV6-RUNX1–like	.06	0.70 (0.38-1.04)	.08	1.22 (0.99-1.48)	.06	0.98 (0.78-1.20)	.87	1.18 (0.81-1.56)	.35
ZNF384	.004^d	1.08 (0.76-1.45)	.63	1.09 (0.81-1.40)	.55	1.40 (1.18-1.66)	<.001^d	1.15 (0.73-1.60)	.49
MEF2D	.004^d	1.37 (1.06-1.74)	.02	1.14 (0.85-1.47)	.36	1.08 (0.79-1.37)	.59	0.04 (2.45E-07-1.04)	.06
Near haploid	.09	1.05 (0.74-1.41)	.76	0.56 (0.24-0.93)	.02	0.84 (0.58-1.10)	.22	1.08 (0.62-1.54)	.74
Low hypodiploid	.48	1.30 (0.91-1.77)	.14	1.09 (0.74-1.51)	.63	0.95 (0.62-1.31)	.77	0.92 (0.20-1.59)	.82
PAX5 P80R	.17	0.85 (0.40-1.36)	.55	1.24 (0.89-1.66)	.19	0.70 (0.32-1.08)	.12	1.25 (0.69-1.84)	.38
NUTM1	.67	1.42 (0.89-2.12)	.13	1.09 (0.61-1.71)	.73	1.20 (0.82-1.69)	.33	1.39 (0.68-2.19)	.29
T-ALL^e	<.001^d	1.22 (1.07-1.37)	.003^d	0.53 (0.40-0.67)	<.001^d	0.80 (0.71-0.90)	<.001^d	0.97 (0.79-1.16)	.76

Abbreviations: OR, odds ratio; B-ALL, B-cell acute lymphoblastic leukemia; T-ALL, T-cell acute lymphoblastic leukemia.

^{^a}

Derived from the Firth multiple logistic regression model. Overall subtype P values were determined by likelihood ratio test, and the Bonferroni-adjusted P value threshold is .003. For individual subtype-ancestry assessment, P values were determined by the Wald test, and the Bonferroni-adjusted threshold for significance is .01.

^{^b}

Percentage genetic ancestry assessed as a continuous variable, with each ancestry varying from 0% to 100%. The 4 non-European ancestries were included in the model, leaving European ancestry out as the reference.

^{^c}

ORs represent intervals of every 25% increase; for example, for every 25% increase in Native American ancestry with corresponding 25% decrease in European ancestry (and remainder of ancestries fixed), there is a 1.48-fold increase in the odds of developing CRLF2-rearranged ALL.

^{^d}

Significant after correction for multiple testing.

^{^e}

T-ALL evaluated within Ma-Spore, St Jude, and Guatemala cohorts only, as these were unselected cohorts that treated both B-ALL and T-ALL.