Table 1 Examples of germline genetic... | American Society of Hematology

Table 1

Examples of germline genetic variants associated with ALL susceptibility, treatment outcomes, and toxicities of ALL therapy

Gene	SNP ID	Study design	Phenotype	Sample size (N)	Odds ratio (95% CI)	P	Reference
ALL susceptibility
ARID5B	rs7089424	GWAS	ALL risk	907	1.65 (1.54-1.76)	6.7 × 10⁻¹⁹	27
ARID5B	rs10821936	GWAS	ALL risk	441	1.91 (1.6-2.2)	1.4 × 10⁻¹⁵	28
IKZF1	rs4132601	GWAS	ALL risk	907	1.69 (1.58-1.81)	1.2 × 10⁻¹⁹	27
IKZF1	rs11978267	GWAS	ALL risk	441	1.69 (1.4-1.9)	8.8 × 10⁻¹¹	28
CEBPE	rs2239633	GWAS	ALL risk	907	1.34 (1.22-1.45)	2.9 × 10⁻⁷	27
CDKN2A	rs17756311	GWAS	ALL risk	2450	1.36 (1.18-1.56)	1.4 × 10⁻⁵	30
PIP4K2A	rs7088318	GWAS	ALL risk	2450	1.40 (1.28-1.53)	1.1 × 10⁻¹¹	30
GATA3	rs3824662	GWAS	ALL risk	3107	1.31 (1.21-1.41)	8.6 × 10⁻¹²	31
GATA3	rs3824662	GWAS	Risk for Ph-like ALL	511	3.85 (2.7-5.4)	2.2 × 10⁻¹⁴	32
TP63	rs17505102	GWAS	Risk for ETV6-RUNX1 ALL	1370	0.65 (0.52-0.75)	8.9 × 10⁻⁹	39
Treatment outcome
TPMT	rs1800462	Candidate gene	Minimal residual disease	814	0.34 (0.13-0.86)	.02	44
	rs1800460
	rs1142345
	rs1800460	Candidate gene	Relapse	601	0.36 (0.15-0.88)	.03	45
	rs1142345	Candidate gene	Relapse	601	0.36 (0.15-0.88)	.03	45
IL15	rs17007695	GWAS	Minimal residual disease	487	2.67 (1.53-4.68)	8.9 × 10⁻⁷	55
PYGL	rs7142143	GWAS	Relapse	2535	3.61 (2.34-5.57)	6.7 × 10⁻⁹	58
PDE4B	rs6683977	GWAS	Relapse	2535	1.41 (1.22-1.64)	5.1 × 10⁻⁶	58
GATA3	rs3824662	GWAS	Relapse	781	1.43 (1.10-1.86)	.007	32
		GWAS	Minimal residual disease	710	1.38 (1.03-1.83)	.039	32
		GWAS	Relapse	2258	2.0 (1.71-3.66)	2.3 × 10⁻⁶	31
Toxicities
TPMT	rs1800462	Candidate gene	Thiopurine-induced myelosuppression	180	9.3 (3.58-24.27)	.007	68
	rs1800460
	rs1142345
NUDT15	rs116855232	GWAS	Thiopurine intolerance	657	*	8.8 × 10⁻⁹	70
ACP1	rs12714403	GWAS	Glucocorticoid-induced osteonecrosis	362	5.6 (2.7-11.3)	1.9 × 10⁻⁶	80
GRIA1	rs4958351	GWAS	Asparaginase allergy	485	1.75 (1.41-2.17)	3.5 × 10⁻⁷	84
HLA-DRB1	HLA-DRB1*07:01	Candidate gene	Asparaginase allergy	1870	1.64 (1.28-2.09)	7.5 × 10⁻⁵	86
HLA-DRB1	HLA-DRB1*07:01	Candidate gene	Anti-asparaginase antibody	502	2.92 (1.82-4.80)	1.4 × 10⁻⁵	86
ASNS	rs3832526	Candidate gene	Asparaginase allergy	533	14.6 (3.6-58.7)	<.0005	87
ASNS	rs3832526	Candidate gene	Asparaginase pancreatitis	533	8.6 (2.0-37.3)	.008	87
CBR3	rs1056892	Candidate gene	Anthracycline-induced cardiomyopathy	487	1.79 (1.08-2.96)	.02	88
HAS3	rs2232228	GWAS	Anthracycline-induced cardiomyopathy	362	3.7 (1.3-10.2)	.05	89
CEP72	rs924607	GWAS	Vincristine-induced neuropathy	321	*	4.7 × 10⁻⁸	90
SLCO1B1	rs11045879	GWAS	Methotrexate clearance	640	*	8.2 × 10⁻¹¹	104, 105
		GWAS	Methotrexate-induced GI toxicity	206	16.4 (8.7-26.7)	.004	104, 105
		Candidate gene	Methotrexate clearance	115	*	.008	106
	rs4149056	Candidate gene	Methotrexate clearance	415	*	3.5 × 10⁻⁴	50

Gene	SNP ID	Study design	Phenotype	Sample size (N)	Odds ratio (95% CI)	P	Reference
ALL susceptibility
ARID5B	rs7089424	GWAS	ALL risk	907	1.65 (1.54-1.76)	6.7 × 10⁻¹⁹	27
ARID5B	rs10821936	GWAS	ALL risk	441	1.91 (1.6-2.2)	1.4 × 10⁻¹⁵	28
IKZF1	rs4132601	GWAS	ALL risk	907	1.69 (1.58-1.81)	1.2 × 10⁻¹⁹	27
IKZF1	rs11978267	GWAS	ALL risk	441	1.69 (1.4-1.9)	8.8 × 10⁻¹¹	28
CEBPE	rs2239633	GWAS	ALL risk	907	1.34 (1.22-1.45)	2.9 × 10⁻⁷	27
CDKN2A	rs17756311	GWAS	ALL risk	2450	1.36 (1.18-1.56)	1.4 × 10⁻⁵	30
PIP4K2A	rs7088318	GWAS	ALL risk	2450	1.40 (1.28-1.53)	1.1 × 10⁻¹¹	30
GATA3	rs3824662	GWAS	ALL risk	3107	1.31 (1.21-1.41)	8.6 × 10⁻¹²	31
GATA3	rs3824662	GWAS	Risk for Ph-like ALL	511	3.85 (2.7-5.4)	2.2 × 10⁻¹⁴	32
TP63	rs17505102	GWAS	Risk for ETV6-RUNX1 ALL	1370	0.65 (0.52-0.75)	8.9 × 10⁻⁹	39
Treatment outcome
TPMT	rs1800462	Candidate gene	Minimal residual disease	814	0.34 (0.13-0.86)	.02	44
	rs1800460
	rs1142345
	rs1800460	Candidate gene	Relapse	601	0.36 (0.15-0.88)	.03	45
	rs1142345	Candidate gene	Relapse	601	0.36 (0.15-0.88)	.03	45
IL15	rs17007695	GWAS	Minimal residual disease	487	2.67 (1.53-4.68)	8.9 × 10⁻⁷	55
PYGL	rs7142143	GWAS	Relapse	2535	3.61 (2.34-5.57)	6.7 × 10⁻⁹	58
PDE4B	rs6683977	GWAS	Relapse	2535	1.41 (1.22-1.64)	5.1 × 10⁻⁶	58
GATA3	rs3824662	GWAS	Relapse	781	1.43 (1.10-1.86)	.007	32
		GWAS	Minimal residual disease	710	1.38 (1.03-1.83)	.039	32
		GWAS	Relapse	2258	2.0 (1.71-3.66)	2.3 × 10⁻⁶	31
Toxicities
TPMT	rs1800462	Candidate gene	Thiopurine-induced myelosuppression	180	9.3 (3.58-24.27)	.007	68
	rs1800460
	rs1142345
NUDT15	rs116855232	GWAS	Thiopurine intolerance	657	*	8.8 × 10⁻⁹	70
ACP1	rs12714403	GWAS	Glucocorticoid-induced osteonecrosis	362	5.6 (2.7-11.3)	1.9 × 10⁻⁶	80
GRIA1	rs4958351	GWAS	Asparaginase allergy	485	1.75 (1.41-2.17)	3.5 × 10⁻⁷	84
HLA-DRB1	HLA-DRB1*07:01	Candidate gene	Asparaginase allergy	1870	1.64 (1.28-2.09)	7.5 × 10⁻⁵	86
HLA-DRB1	HLA-DRB1*07:01	Candidate gene	Anti-asparaginase antibody	502	2.92 (1.82-4.80)	1.4 × 10⁻⁵	86
ASNS	rs3832526	Candidate gene	Asparaginase allergy	533	14.6 (3.6-58.7)	<.0005	87
ASNS	rs3832526	Candidate gene	Asparaginase pancreatitis	533	8.6 (2.0-37.3)	.008	87
CBR3	rs1056892	Candidate gene	Anthracycline-induced cardiomyopathy	487	1.79 (1.08-2.96)	.02	88
HAS3	rs2232228	GWAS	Anthracycline-induced cardiomyopathy	362	3.7 (1.3-10.2)	.05	89
CEP72	rs924607	GWAS	Vincristine-induced neuropathy	321	*	4.7 × 10⁻⁸	90
SLCO1B1	rs11045879	GWAS	Methotrexate clearance	640	*	8.2 × 10⁻¹¹	104, 105
		GWAS	Methotrexate-induced GI toxicity	206	16.4 (8.7-26.7)	.004	104, 105
		Candidate gene	Methotrexate clearance	115	*	.008	106
	rs4149056	Candidate gene	Methotrexate clearance	415	*	3.5 × 10⁻⁴	50

CI, confidence interval; GI, gastrointestinal; GWAS, genome-wide association study; ID, identification; Ph, Philadelphia chromosome; SNP, single-nucleotide polymorphism.

View Large

This Feature Is Available To Subscribers Only