Leptin rs7799039 (G2548A) polymorphism is associated with cancer risk: a meta-analysis involving 25,799 subjects

Figures & data

Table 1 Characteristics of the studies in meta-analysis

Study	Publication year	Country	Ethnicity	Cancer type	Sample size (case/control)	Source of control	Genotype method
Ribeiro et al.^Citation26	2004	Portugal	Caucasians	Prostate cancer	150/118	HB	PCR-RFLP
Skibola et al.^Citation27	2004	USA	Caucasians	Lymphoma	376/805	PB	TaqMan
Willett et al.^Citation28	2005	UK	Caucasians	Lymphoma	593/754	PB	TaqMan
Snoussi et al.^Citation51	2006	Tunisia	Mixed	Breast cancer	308/222	HB	PCR-RFLP
Slattery et al.^Citation52	2008	USA	Mixed	Colorectal cancer	1565/1965	HB	TaqMan
Chovanec et al.^Citation29	2009	Czech	Caucasians	Endometrial cancer	66/543	HB	PCR
Moore et al.^Citation30	2009	Finland	Caucasians	Prostate cancer	1053/1053	PB	TaqMan
Pechlivanis et al.^Citation31	2009	Czech	Caucasians	Colorectal cancer	702/752	HB	TaqMan
Vasku et al.^Citation32	2009	Czech	Caucasians	Colorectal cancer	102/101	HB	PCR-sequencing
Cleveland et al.^Citation33	2010	USA	Caucasians	Breast cancer	1059/1101	PB	PCR
Kim et al.^Citation21	2012	Korea	Asians	Gastric cancer	48/48	HB	PCR-RFLP
Ribeiro et al.^Citation34	2012	Portugal	Caucasians	Prostate cancer	449/557	HB	TaqMan
Tavil et al.^Citation35	2012	Turkey	Caucasians	Leukemia	72/70	HB	PCR-RFLP
Garcia-Robles et al.^Citation53	2013	Mexico	Mixed	Breast cancer	130/189	HB	PCR
Unsal et al.^Citation36	2014	Turkey	Caucasians	Lung cancer	162/130	HB	PCR-RFLP
Zhang et al.^Citation45	2018	China	Asians	Hepatocellular carcinoma	584/923	HB	SNPscan
Hussain et al.^Citation46	2015	India	Asians	Oral cancer	306/228	HB	PCR-RFLP
Karakus et al.^Citation37	2015	Turkey	Caucasians	Breast cancer	199/185	PB	PCR
Mahmoudi et al.^Citation38	2015	Iran	Caucasians	Breast cancer	45/41	PB	PCR-RFLP
Mohammadzadeh et al.^Citation39	2015	Iran	Caucasians	Breast cancer	100/100	HB	PCR-RFLP
Rostami et al.^Citation40	2015	Iran	Caucasians	Breast cancer	203/171	HB	PCR-RFLP
Mahmoudi et al.^Citation41	2016	Iran	Caucasians	Colorectal cancer	261/339	HB	PCR-RFLP
Amer et al.^Citation42	2017	Egypt	Caucasians	Hepatocellular carcinoma	150/100	HB	PCR-RFLP
Ali et al.^Citation43	2017	Pakistan	Caucasians	Bladder carcinoma	200/200	PB	PCR
Qiu et al.^Citation47	2017	China	Asians	Esophageal cancer	507/1496	HB	SNPscan
Rodrigo et al.^Citation44	2017	Sri Lanka	Caucasians	Breast cancer	80/80	PB	PCR
Cao et al.^Citation54	2015	China	Asians	Lung cancer	162/200	HB	PCR-RFLP
Yuan et al.^Citation48	2017	China	Asians	Breast cancer	703/805	HB	MALDI-TOF MS
Liu et al.^Citation49	2018	China	Asians	Breast cancer	434/440	HB	MALDI-TOF MS
Liu et al.^Citation49	2018	China	Asians	Breast cancer	334/331	HB	MALDI-TOF MS
Zhang et al.^Citation50	2014	USA	Mixed	Pancreatic cancer	173/476	PB	TaqMan

Abbreviations: PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; PCR, polymerase chain reaction; MALDI-TOF MS, Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry.

Table 2 Distribution of LEP rs7799039 G>A polymorphism genotype and allele

Study	Publication year	Case AA	Case AG	Case GG	Control AA	Control AG	Control GG	Case A	Case G	Control A	Control G	HWE
Ribeiro et al.^Citation26	2004	24	89	30	12	62	44	137	149	86	150	Yes
Skibola et al.^Citation27	2004	91	167	118	167	376	259	349	403	710	894	Yes
Willett et al.^Citation28	2005	127	294	170	145	348	260	548	634	638	868	Yes
Snoussi et al.^Citation51	2006	37	152	119	11	99	112	226	390	121	323	Yes
Slattery et al.^Citation52	2008	284	782	499	393	938	634	1350	1780	1724	2206	Yes
Chovanec et al.^Citation29	2009	20	33	13	131	255	149	73	59	517	553	Yes
Moore et al.^Citation30	2009	281	453	213	216	437	210	1015	879	869	857	Yes
Pechlivanis et al.^Citation31	2009	120	309	230	150	334	227	549	769	634	788	Yes
Vasku et al.^Citation32	2009	24	41	35	20	44	36	89	111	84	116	Yes
Cleveland et al.^Citation33	2010	226	492	341	180	561	360	944	1174	921	1281	Yes
Kim et al.^Citation21	2012	29	18	1	33	14	1	76	20	80	16	Yes
Ribeiro et al.^Citation34	2012	73	212	164	84	268	203	358	540	436	674	Yes
Tavil et al.^Citation35	2012	26	31	15	27	29	14	83	61	83	57	Yes
Garcia-Robles et al.^Citation53	2013	22	71	37	46	95	48	115	145	187	191	Yes
Unsal et al.^Citation36	2014	50	86	26	27	63	40	186	138	117	143	Yes
Zhang et al.^Citation45	2014	AA+AG:122	-	51	AA+AG:318	-	158	-	-	-	-	Yes
Hussain et al.^Citation46	2015	50	154	102	23	92	113	254	358	138	318	Yes
Karakus et al.^Citation37	2015	49	105	45	47	98	40	203	195	192	178	Yes
Mahmoudi et al.^Citation38	2015	27	11	7	17	19	5	65	25	53	29	Yes
Mohammadzadeh et al.^Citation39	2015	36	55	9	52	45	3	127	73	149	51	Yes
Rostami et al.^Citation40	2015	115	64	24	63	77	31	294	112	203	139	Yes
Cao et al.^Citation54	2015	57	75	30	33	80	87	189	135	146	254	Yes
Mahmoudi et al.^Citation41	2016	76	135	50	113	154	72	287	235	380	298	Yes
Amer et al.^Citation42	2017	60	69	21	49	47	4	189	111	145	55	Yes
Ali et al.^Citation43	2017	61	103	36	61	100	39	225	175	222	178	Yes
Qiu et al.^Citation47	2017	291	184	29	797	591	101	766	242	2185	793	Yes
Rodrigo et al.^Citation44	2017	32	43	5	53	24	3	107	53	130	30	Yes
Yuan et al.^Citation48	2017	416	GG+GA:276	-	426	GG+GA:347	-	-	-	-	-	Yes
Zhang et al.^Citation50	2018	295	221	59	505	360	56	811	339	1370	472	Yes
Liu et al.^Citation49	2018	252	GG+GA:182	-	236	GG+GA:206	-	-	-	-	-	Yes
Liu et al.^Citation49	2018	201	GG+GA:133	-	190	GG+GA:141	-	-	-	-	-	Yes

Abbreviation: HWE, Hardy–Weinberg equilibrium.

Figure 1 Flow diagram of the meta-analysis of the association between LEP rs7799039 G>A polymorphism and overall cancer risk.

Table 3 Results of the meta-analysis from different genetic models

	No. of cases/controls	A vs G				AA vs GG				AA+GA vs GG				AA vs.GA+GG
		OR (95% CI)	P	I^2	P (Q-test)	OR (95% CI)	P	I^2	P (Q-test)	OR (95% CI)	P	I^2	P (Q-test)	OR (95% CI)	P	I^2	P (Q-test)
Total	11,276/14,523	1.10(0.1.00–1.21)	0.051	79.1%	<0.001	1.22(1.01–1.48)	0.042	74.9%	<0.001	1.16(1.02–1.33)	0.026	68.3%	<0.001	1.12(1.00–1.26)	0.059	69.6%	<0.001
Ethnicity
Caucasians	6,022/7,200	1.07(0.96–1.18)	0.216	69.5%	<0.001	1.18(0.98–1.41)	0.088	58.5%	0.001	1.11(0.97–1.27)	0.122	49.2%	0.008	1.09(0.92–1.28)	0.314	67.2%	<0.001
Mixed	2,176/2,852	1.07(0.78–1.47)	0.687	83.9%	0.002	1.17(0.55–2.48)	0.676	83.9%	0.002	1.14(0.90–1.45)	0.279	56.4%	0.076	1.08(0.58–2.00)	0.816	81.0%	0.005
Asians	3,078/4,471	1.27(0.87–1.87)	0.216	91.7%	<0.001	1.60(0.67–3.80)	0.287	90.6%	<0.001	1.42(0.71–2.85)	0.326	89.6%	<0.001	1.23(1.01–1.49)	0.044	70.0%	0.001
Cancer type
Prostate cancer	1,652/1,728	1.17(0.97–1.40)	0.098	59.5%	0.085	1.36(0.94–1.97)	0.106	56.8%	0.099	1.24(0.89–1.72)	0.208	70.7%	0.033	1.24(1.04–1.47)	0.014	0.0%	0.470
Breast cancer	3,595/3,665	1.02(0.79–1.31)	0.878	82.4%	<0.001	1.11(0.70–1.75)	0.669	71.3%	0.001	1.07(0.84–1.38)	0.576	46.1%	0.072	1.12(0.87–1.43)	0.385	78.3%	<0.001
Colorectal cancer	2,630/3,157	0.95(0.88–1.03)	0.203	0.0%	0.671	0.90(0.77–1.05)	0.169	0.0%	0.675	0.99(0.88–1.11)	0.849	0.0%	0.615	0.88(0.77–1.00)	0.046	0.0%	0.699
Others	3,399/5,973	1.17(0.98–1.40)	0.081	82.7%	<0.001	1.34(0.92–1.94)	0.127	81.1%	<0.001	1.25(0.95–1.65)	0.104	78.2%	<0.001	1.18(0.98–1.42)	0.083	63.0%	0.002
System of cancer
Reproductive and breast cancer	5,313/5,936	1.10(0.95–1.29)	0.207	75.9%	<0.001	1.28(0.98–1.68)	0.074	63.0%	0.002	1.15(0.97–1.37)	0.105	47.9%	0.032	1.17(0.97–1.40)	0.096	70.7%	<0.001
Hematopoietic malignancy	1,041/1,629	1.13(1.01–1.26)	0.038	0.0%	0.595	1.25(1.00–1.55)	0.049	0.0%	0.680	1.17(0.99–1.39)	0.068	0.0%	0.399	1.15(0.95–1.39)	0.140	0.0%	0.730
Digestive system cancer	4,398/6,428	0.99(0.86–1.13)	0.838	73.4%	<0.001	0.94(0.70–1.25)	0.658	70.4%	0.001	1.01(0.81–1.27)	0.928	71.7%	<0.001	0.95(0.82–1.09)	0.454	47.5%	0.055
Others	524/530	1.60(0.96–2.66)	0.070	88.2%	<0.001	2.48(0.99–6.23)	0.053	85.1%	0.001	2.06(1.05–4.02)	0.035	80.3%	0.006	1.66(0.90–3.03)	0.102	78.6%	0.009
Sample size
<1000	3,685/4,312	1.13(0.94–1.37)	0.200	81.6%	<0.001	1.32(0.92–1.90)	0.129	74.8%	<0.001	1.29(1.03–1.62)	0.027	64.3%	<0.001	1.15(0.92–1.43)	0.224	73.3%	<0.001
≥1000	7,591/10,211	1.04(0.96–1.12)	0.378	62.4%	0.006	1.05(0.88–1.26)	0.559	67.9%	0.002	1.01(0.90–1.13)	0.836	51.2%	0.037	1.09(0.97–1.23)	0.135	61.6%	0.005
Source of control
Hospital-based	7,498/9,828	1.13(0.98–1.30)	0.087	83.6%	<0.001	1.26(0.94–1.68)	0.118	81.3%	<0.001	1.21(0.98–1.49)	0.073	77.7%	<0.001	1.13(0.98–1.31)	0.100	71.1%	<0.001
Population-based	3,778/4,695	1.08(0.97–1.19)	0.151	47.6%	0.064	1.24(1.09–1.42)	0.001	0.0%	0.731	1.10(0.99–1.21)	0.069	0.0%	0.811	1.11(0.90–1.37)	0.314	65.2%	0.005

Figure 2 Meta-analysis of the association between LEP rs7799039 G>A polymorphism and overall cancer risk (dominant model, random-effects model).

Figure 3 Begg’s funnel plot of meta-analysis of the association between LEP rs7799039 G>A polymorphism and cancer risk (dominant genetic model, random-effects model).

Figure 4 Sensitivity analysis of the influence of dominant model (random-effects estimates).

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