MDM2 promoter del1518 polymorphism and cancer risk: evidence from 22,931 subjects

Figures & data

Figure 1 Flowchart of selection of studies included in the current meta-analysis for the correlation between MDM2 del1518 polymorphism and overall cancer susceptibility.

Abbreviation: CBM, Chinese Biomedical.

Table 1 Characteristics of studies included in the current meta-analysis

Surname	Year	Cancer type	Country	Ethnicity	Design	Genotype method	Males (%), case/control	Case				Control				MAF	HWE	Score
								II	ID	DD	All	II	ID	DD	All
Hu	2006	Lung	China	Asian	PB	PCR	73.5/72.7	349	317	51	717	523	464	96	1,083	0.30	0.631	13
Ma	2006	Breast	China	Asian	PB	PCR	0.0/0.0	179	157	30	366	305	241	59	605	0.30	0.263	9
Cao	2007	ESCC	China	Asian	PB	PCR	67.2/64.6	181	146	24	351	310	285	47	642	0.30	0.090	11
Cao	2007	Gastric	China	Asian	PB	PCR	63.2/64.6	132	72	8	212	310	285	47	642	0.30	0.090	11
Jin	2008	Colorectal	China	Asian	PB	PCR	NA/NA	25	80	95	200	182	319	339	840	0.59	<0.001	12
Kang	2009	Ovarian	China	Asian	HB	PCR	0.0/0.0	132	106	19	257	122	115	20	257	0.30	0.318	9
Dong	2012	HCC	China	Asian	PB	PCR	65.7/65.0	169	199	52	420	206	178	39	423	0.30	0.951	12
Ma	2012	ESCC	China	Asian	PB	PCR	55.8/55.8	120	91	15	226	118	92	16	226	0.27	0.736	10
Salimi	2015	UL	Iran	Caucasian	PB	PCR	0.0/0.0	71	60	23	154	119	64	14	197	0.23	0.195	9
Zhang	2015	ESCC	China	Asian	HB	PCR	50.8/56.1	17	59	56	132	13	48	71	132	0.72	0.257	9
Gansmo	2016	Colorectal	Norway	Caucasian	PB	PCR	49.2/50.1	478	775	279	1,532	1,285	1,777	687	3,749	0.42	0.095	12
Gansmo	2016	Lung	Norway	Caucasian	PB	PCR	62.7/50.1	447	624	260	1,331	1,285	1,777	687	3,749	0.42	0.095	12
Gansmo	2016	Breast	Norway	Caucasian	PB	PCR	0.0/0.0	581	809	327	1,717	1,285	1,777	687	3,749	0.42	0.095	12
Gansmo	2016	Prostate	Norway	Caucasian	PB	PCR	100.0/100.0	836	1,240	425	2,501	1,285	1,777	687	3,749	0.42	0.095	12
Gansmo	2017	Ovarian	Norway	Caucasian	HB	PCR	0.0/0.0	484	655	246	1,385	636	877	359	1,872	0.43	0.069	12
Gansmo	2017	Endometrial	Norway	Caucasian	HB	PCR	0.0/0.0	492	664	248	1,404	636	877	359	1,872	0.43	0.069	12

Abbreviations: HB, hospital based; HCC, hepatocellular carcinoma; HWE, Hardy–Weinberg equilibrium; ESCC, esophageal squamous cell carcinoma; MAF, minor allele frequency; NA, not available; PB, population based; PCR, polymerase chain reaction; UL, uterine leiomyoma; II, Ins/Ins; DD, Del/Del; ID, Ins/Del.

Figure 2 Forest plots of effect estimates for MDM2 del1518 polymorphism and overall cancer susceptibility under dominant model (ID + DD vs II).

Notes: For each study, the estimation of OR and its 95% CI is plotted with a box and a horizontal line. The diamonds represent the pooled ORs and 95% CIs. Weights are from random effects analysis.
Abbreviations: CIs, confidence intervals; ORs, odds ratios; ID, Ins/Del; II, Ins/Ins; DD, Del/Del.

Table 2 Meta-analysis of the association between MDM2 del1518 (rs3730485) polymorphism and overall cancer risk

Variables	Number of studies	Homozygous		Heterozygous		Recessive		Dominant		Allele
		DD vs II		ID vs II		DD vs ID + II		ID + DD vs II		D vs I
		OR (95% CI)	P^het	OR (95% CI)	P^het	OR (95% CI)	P^het	OR (95% CI)	P^het	OR (95% CI)	P^het
All	16	1.01 (0.90–1.14)	0.003	1.03 (0.96–1.12)	0.009	0.98 (0.90–1.07)	0.049	1.03 (0.94–1.12)	<0.001	1.01 (0.94–1.07)	<0.001
Cancer type
Lung	2	0.97 (0.72–1.30)	0.133	1.01 (0.90–1.14)	0.909	0.96 (0.71–1.30)	0.108	1.02 (0.91–1.13)	0.694	1.01 (0.94–1.10)	0.303
Breast	2	1.03 (0.88–1.20)	0.449	1.03 (0.91–1.15)	0.526	1.03 (0.89–1.18)	0.333	1.03 (0.92–1.15)	0.780	1.02 (0.95–1.10)	0.822
ESCC	3	0.82 (0.56–1.19)	0.700	0.91 (0.74–1.13)	0.909	0.79 (0.58–1.08)	0.500	0.89 (0.73–1.10)	0.809	0.89 (0.76–1.04)	0.428
Others	5	1.07 (0.78–1.48)	0.001	1.04 (0.84–1.29)	0.001	1.01 (0.79–1.29)	0.015	1.05 (0.83–1.33)	<0.001	1.03 (0.86–1.24)	<0.001
Colorectal	2	1.43 (0.78–2.63)	0.016	1.37 (0.91–2.08)	0.084	1.12 (0.84–1.49)	0.091	1.42 (0.86–2.36)	0.029	1.20 (0.91–1.60)	0.020
Ovarian	2	0.90 (0.74–1.09)	0.944	0.96 (0.83–1.11)	0.480	0.91 (0.77–1.09)	0.911	0.94 (0.82–1.08)	0.556	0.95 (0.86–1.04)	0.708
Ethnicity
Asians	9	0.95 (0.70–1.29)	0.005	1.01 (0.84–1.21)	0.004	0.92 (0.74–1.15)	0.071	0.99 (0.81–1.21)	<0.001	0.96 (0.83–1.12)	<0.001
Caucasians	7	1.02 (0.91–1.13)	0.055	1.05 (0.98–1.12)	0.246	0.99 (0.90–1.08)	0.104	1.04 (0.97–1.12)	0.082	1.02 (0.96–1.08)	0.020
Source of control
PB	12	1.07 (0.92–1.24)	0.002	1.06 (0.96–1.17)	0.003	1.02 (0.92–1.14)	0.048	1.06 (0.95–1.18)	<0.001	1.04 (0.96–1.12)	<0.001
HB	4	0.89 (0.77–1.02)	0.822	0.97 (0.87–1.07)	0.911	0.89 (0.79–1.00)	0.570	0.94 (0.86–1.04)	0.859	0.94 (0.88–1.00)	0.517
Quality score
≥12	9	1.04 (0.92–1.16)	0.015	1.06 (0.99–1.14)	0.108	0.99 (0.92–1.08)	0.127	1.06 (0.98–1.14)	0.025	1.03 (0.97–1.09)	0.010
<12	7	0.89 (0.61–1.30)	0.026	0.94 (0.75–1.16)	0.027	0.89 (0.65–1.21)	0.080	0.93 (0.73–1.18)	0.003	0.93 (0.76–1.14)	<0.001
Bias			0.919		0.921		0.920		0.921		0.990

Abbreviations: CI, confidence interval; DD, Del/Del; ESCC, esophageal squamous cell carcinoma; HB, hospital based; het, heterogeneity; ID, Ins/Del; II, Ins/Ins; OR, odds ratio; PB, population based.

Figure 3 Funnel plot to detect publication bias for MDM2 del1518 polymorphism and overall cancer susceptibility under dominant model.

Note: Each point represents a separate study for the indicated association.
Abbreviation: ES, effect size.

Table S1 Score of quality assessment

Criteria	Score
Representativeness of cases
Selected from population cancer registry	2
Selected from hospital	1
No method of selection described	0
Representativeness of controls
Population based	3
Blood donors	2
Hospital based	1
Not described	0
Ascertainment of cancer cases
Histopathologic confirmation	2
Patient medical record	1
Not described	0
Control selection
Controls matched with cases by age and sex	2
Controls matched with cases only by age or by sex	1
Not matched or not descried	0
Genotyping examination
Genotyping done blindly and quality control	2
Only genotyping done blindly or quality control	1
Unblinded and without quality control	0
Total sample size for both cases and controls
>1,000	3
>500 but <1,000	2
>200 but <500	1
<200	0