Associations of NQO1 C609T and NQO1 C465T polymorphisms with acute leukemia risk: a PRISMA-compliant meta-analysis

Figures & data

Figure 1 Flow diagram of the study selection process.

Abbreviations: NQO1, NAD(P)H:quinone oxidoreductase; AL, acute leukemia; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia.

Table 1 Characteristics of included studies

Study	Year	Ethnicity	Sample size		Age	Genotyping method	Control sources	Polymorphism of NQO1	Cases	P-value for HWE	Quality score
			Cases	Controls
Bolufer et al^Citation3	2007	Caucasian	302 141	454 454	Adult	PCR-based methods	PB	C609T	AML ALL	0.422	8 8
Bonaventure et al^Citation12	2012	Caucasian	433 51	441 441	Children	Imputation	PB	C609T	ALL AML	0.205	8 8
Chan et al^Citation33	2011	Javanese	185	177	Children	PCR–RFLP	PB	C609T	ALL	0.926	7
Clavel et al^Citation30	2005	Mixed	219	105	Children	PCR–RFLP	HB	C609T	ALL	0.673	7
de Aguiar Goncalves et al^Citation28	2012	Mixed	519 107	401 401	Children	PCR	PB	C609T	ALL AML	0.057	8 8
Eguchi-Ishimae et al^Citation9	2005	Asian	103 103	185 185	Children	PCR–RFLP	PB	C609T C465T	ALL AML	0.482	7 7
Eyada et al^Citation13	2007	Caucasian	19 13	11 11	NA	PCR–RFLP	NA	C609T	AML ALL	NA	3 3
Guillem et al^Citation14	2007	Caucasian	81	64	Adult	PCR–RFLP	PB	C609T	AML	0.556	7
Jia et al^Citation2	2012	Asian	102 48	150 150	Adult	LDR	HB	C609T	AML ALL	0.005	5 5
Kracht et al^Citation15	2004	Caucasian	138	190	Children	PCR	PB	C609T	ALL	0.147	8
Krajinovic et al^Citation16	2002	Caucasian	174	323	Children	PCR	PB	C609T C465T	ALL	0.312	7 7
Malik et al^Citation5	2006	Mixed	262	688	Adult	PCR–RFLP	PB	C609T	AML	0.295	7
Naoe et al^Citation26	2000	Asian	411	150	Adult	PCR	PB	C609T	AML	0.037	7
Ouerhani et al^Citation31	2013	African	100	106	Adult	PCR–RFLP	PB	C609T	ALL	0.155	8
Rimando et al^Citation21	2008	Asian	60	60	Children	PCR–CTPP	PB	C609T	ALL	<0.01	6
Seedhouse et al^Citation1	2002	Caucasian	168	178	Adult	PCR–RFLP	PB	C609T	AML	0.12	8
Silveira Vda et al^Citation17	2010	Caucasian	206	364	Children	PCR–RFLP	HB	C609T	ALL	0.218	6
Sirma et al^Citation29	2004	Mixed	189 84	286 286	Children	PCR–RFLP	PB	C609T	ALL AML	0.016	6 6
Sorour et al^Citation32	2013	African	90	60	Adult	PCR–RFLP	PB	C609T	AML	0.299	7
Voso et al^Citation18	2007	Caucasian	160	162	Adult	PCR–RFLP	PB	C609T	AML	0.12	8
Yamaguti et al^Citation20	2009	Caucasian	133	133	Adult	PCR–RFLP	PB	C609T	AML	0.054	6
Yamaguti et al^Citation19	2010	Caucasian	99	99	Children	PCR	PB	C609T	ALL	0.133	6
Yang et al^Citation22	2005	Asian	228	241	Adult	PCR–RFLP	PB	C609T	AML	0.495	6
Zaker et al^Citation23	2011	Asian	140	160	Adult	PCR–RFLP	PB	C609T C465T	AML	0.19 <0.01	9 8
Zaker et al^Citation24	2012	Asian	100	135	Children	PCR–RFLP	PB	C609T C465T	ALL	0.162 <0.01	8 7
Zhang et al^Citation25	2009	Asian	170	458	Adult	PCR–RFLP	PB	C609T	ALL	0.017	7
Xu^Citation10	2010	Asian	78 22	100 100	Adult	PCR–RFLP PCR–LDR	HB	C609T	AML ALL	0.001	6 6
Yang^Citation27	2006	Asian	306	458	Adult	PCR–RFLP	PB	C609T	AML	0.017	7

Abbreviations: AL, acute leukemia; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; HWE, Hardy–Weinberg equilibrium; NQO1, NAD(P)H:quinone oxidoreductase; NA, not available; HB, hospital-based; PB, population-based; PCR, polymerase chain reaction; PCR-CTPP, PCR confronting two-pair primer; LDR, ligase detection reaction; RFLP, restriction fragment length polymorphism.

Figure 2 The associations between NQO1 C609T and the ALL risk. (A) Calculated ORs and 95% CIs for the association. (B) Sensitivity analysis via deletion of each individual study. (C) Cumulative meta-analysis according to publication year. (D) Trim-and-fill plot to correct publication bias.

Note: Weights are from random-effects analysis.
Abbreviations: NQO1, NAD(P)H:quinone oxidoreductase; ALL, acute lymphoblastic leukemia; OR, odds ratio; CI, confidence interval.

Table 2 Subgroup analysis for the association of NQO1 C609T with AL risk

Association	Factors	Subgroups	N	OR	95% CI	P-valuea	I^2 (%)
C609T and ALL	Ethnicity	Caucasians	6	1.20	0.94–1.53	0.005	70
		Asians	6	1.25	0.78–2.00	<0.00001	86
		Mix	3	0.98	0.79–1.22	0.12	32
		Javanese	1	1.16	0.85–1.56	NA	NA
		African	1	1.57	1.01–2.44	NA	NA
	Age	Children	12	1.03	0.87–1.22	0.001	64
		Adult	5	1.71	1.20–2.43	0.003	75
	Control source	PB	13	1.12	0.96–1.30	0.001	63
		HB	4	1.59	0.83–3.05	<0.00001	89
C609T and AML	Ethnicity	Caucasians	7	1.02	0.83–1.26	0.14	40
		Asians	7	1.34	1.03–1.74	0.0002	77
		Mix	3	0.83	0.58–1.19	0.05	66
		African	1	1.06	0.58–1.94	NA	NA
	Age	Children	4	0.80	0.63–1.01	0.4	0
		Adult	13	1.19	1.00–1.42	<0.0001	72
	Control source	PB	15	1.03	0.88–1.21	<0.0001	67
		HB	2	1.92	1.45–2.55	0.81	0

Note:

a P-value for heterogeneity test.

Abbreviations: AL, acute leukemia; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CI, confidence interval; N, numbers of comparisons; NA, not available; NQO1, NAD(P)H:quinone oxidoreductase; OR, odds ratio; HB, hospital-based; PB, population-based; NA, not available.

Figure 3 The associations between NQO1 C609T and AML risk. (A) Calculated ORs and 95% CIs for the association. (B) Funnel plot for detecting publication bias.

Note: Weights are from random-effects analysis.
Abbreviations: NQO1, NAD(P)H:quinone oxidoreductase; AML, acute myeloid leukemia; OR, odds ratio; CI, confidence interval.

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