Association between NR5A2 and the risk of pancreatic cancer, especially among Caucasians: a meta-analysis of case–control studies

Figures & data

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

Author		Year	Country	Control source	Case			Control			Sample sizea	Biologic sample	Genotyping method	Completionb	HWE
rs3790843					GG	AG	AA	GG	AG	AA
1	Makoto et al^Citation18	2015	Japan	HB	30	155	175	25	157	218	N	Blood	Fluidgm	Y	0.64
2	Hongwei et al^Citation19	2011	USA	HB	552	410	79	541	478	114	Y	Blood	TapMan	Y	0.81
3	Cosmeri et al^Citation20
	Liverpool	2011	England	PB	60	43	7	72	55	9	N	Tissue/blood	KASPar/Beadchip	N	0.85
	Heldelberg	2011	Germany	PB	324	216	34	594	454	88	Y	Tissue/blood	KASPar	N	0.8
4	Yao^Citation22	2013	China	PB	11	56	60	11	58	58	N	Blood	TapMan	N	0.84
rs3790844					TT	CT	CC	TT	CT	CC
1	Makoto et al^Citation18	2015	Japan	HB	40	165	155	27	163	210	N	Blood	Fluidgm	Y	0.54
2	Hongwei et al^Citation19	2011	USA	HB	670	330	55	652	409	75	Y	Blood	TapMan	Y	0.32
3	Cosmeri et al^Citation20
	Liverpool	2011	England	PB	71	34	4	85	46	5	N	Tissue/blood	KASPar/Beadchip	N	0.69
	Heldelberg	2011	Germany	PB	343	166	25	671	398	57	Y	Tissue/blood	KASPar	N	0.84
4	Alison et al^Citation21	2013	USA	HB	1,319	605	82	1,273	798	137	Y	–	Illumina	Y	0.43
5	Yao^Citation22	2013	China	PB	11	63	53	9	61	57	N	Blood	TapMan	N	0.22
rs12029406					CC	CT	TT	CC	CT	TT
1	Hongwei et al^Citation19	2011	USA	HB	401	517	137	401	534	198	Y	Blood	TapMan	Y	0.14
2	Cosmeri et al^Citation20
	Liverpool	2011	England	PB	45	42	12	55	63	18	N	Tissue/blood	KASPar/Beadchip	N	0.65
	Heldelberg	2011	Germany	PB	217	242	82	406	521	187	Y	Tissue/blood	KASPar	N	0.29
3	Yao^Citation22	2013	China	PB	7	50	70	2	46	79	N	Blood	TapMan	N	0.81

Notes:

a “Y” the total sample size is larger than 1,000; “N” the total sample size is smaller than 1,000.

b “Y” the rs3790844 polymorphism is associated with the risk of pancreatic cancer; “N” the rs3790844 polymorphism is not associated with the risk of pancreatic cancer. P>0.05 means the population was from the same Mendelian population.

Abbreviations: HB, hospital-based; HWE, Hardy–Weinberg equilibrium; PB, population-based.

Figure 1 Flowchart of the literature selection process.

Abbreviation: CNKI, China National Knowledge Infrastructure.

Table 2 Meta-analysis results of association between NR5A2 polymorphism and pancreatic cancer risk

rs3790843		GA vs GG			AA vs GG			GA+AA vs GG			AA vs GG+GA			A vs G
Variables	na	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)
Total	5	0.86 (0.76–0.98)	0.992	0.0	0.71 (0.57–0.88)	0.904	0.0	0.83 (0.73–0.94)	0.950	0.0	0.80 (0.67–0.94)	0.766	0.0	0.85 (0.78–0.93)	0.802	0.0
Control source
HB	2	0.84 (0.71–0.99)	0.944	0.0	0.68 (0.52–0.89)	0.963	0.0	0.80 (0.68–0.94)	0.737	0.0	0.76 (0.62–0.94)	0.729	0.0	0.83 (0.74–0.93)	0.934	0.0
PB	3	0.89 (0.73–1.07)	0.951	0.0	0.77 (0.57–0.88)	0.710	0.0	0.86 (0.72–1.04)	0.882	0.0	0.87 (0.65–1.17)	0.552	0.0	0.89 (0.78–1.02)	0.618	0.0
Sample sizec
N	3	0.90 (0.63–1.28)	0.933	0.0	0.78 (0.51–1.21)	0.682	0.0	0.86 (0.61–1.21)	0.760	0.0	0.86 (0.67–1.09)	0.574	0.0	0.89 (0.75–1.06)	0.532	0.0
Y	2	0.85 (0.75–0.98)	0.793	0.0	0.69 (0.54–0.89)	0.874	0.0	0.82 (0.72–0.94)	0.745	0.0	0.74 (0.58–0.94)	0.934	0.0	0.84 (0.76-0.93)	0.757	0.0
Ethnicity
Asian	2	0.86 (0.53–1.40)	0.771	0.0	0.76 (0.47–1.22)	0.426	0.0	0.80 (0.50–1.28)	0.556	0.0	0.85 (0.67–1.09)	0.303	5.7	0.87 (0.72–1.06)	0.292	9.9
Caucasian	3	0.86 (0.76–0.98)	0.912	0.0	0.70 (0.55–0.89)	0.848	0.0	0.83 (0.73–0.94)	0.843	0.0	0.75 (0.59–0.95)	0.886	0.0	0.85 (0.77–0.93)	0.798	0.0
rs3790844		CT vs TT			CC vs TT			CT+CC vs TT			CC vs TT+CT			C vs T
Variables	na	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)
Total	6	0.76 (0.70–0.84)	0.932	0.0	0.65 (0.54–0.78)	0.617	0.0	0.75 (0.68–0.81)	0.699	0.0	0.73 (0.62–0.85)	0.742	0.0	0.78 (0.73–0.84)	0.555	0.0
Control source
HB	3	0.75 (0.67–0.83)	0.781	0.0	0.61 (0.49–0.74)	0.495	0.0	0.73 (0.66–0.80)	0.491	0.0	0.69 (0.58–0.82)	0.718	0.0	0.76 (0.70–0.82)	0.559	0.0
PB	3	0.83 (0.68–1.01)	0.963	0.0	0.85 (0.56–1.28)	0.959	0.0	0.83 (0.68–1.00)	0.958	0.0	0.91 (0.65–1.27)	0.981	0.0	0.87 (0.75–1.02)	0.953	0.0
Sample sizec
N	3	0.79 (0.55–1.12)	0.791	0.0	0.58 (0.38–0.91)	0.562	0.0	0.73 (0.52–1.02)	0.499	0.0	0.74 (0.58–0.94)	0.624	0.0	0.79 (0.66–0.94)	0.460	0.0
Y	3	0.76 (0.70–0.84)	0.658	0.0	0.66 (0.54–0.82)	0.344	6.2	0.75 (0.68–0.82)	0.452	0.0	0.73 (0.63–0.85)	0.411	0.0	0.78 (0.72–0.85)	0.300	16.9
Ethnicity
Asian	2	0.72 (0.45–1.15)	0.702	0.0	0.55 (0.35–0.88)	0.448	0.0	0.63 (0.40–0.98)	0.540	0.0	0.73 (0.57–0.93)	0.390	0.0	0.76 (0.63–0.92)	0.322	0.0
Caucasian	4	0.77 (0.70–0.84)	0.772	0.0	0.67 (0.55–0.82)	0.491	0.0	0.75 (0.68–0.81)	0.569	0.0	0.73 (0.60–0.89)	0.575	0.0	0.78 (0.73–0.85)	0.404	0.0
rs12029406		CT vs CC			TT vs CC			CT+TT vs CC			TT vs CC+CT			T vs C
Variables	na	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)	OR (95% CI)	P-valueb	I^2 (%)
Total	4	0.91 (0.80–1.05)	0.487	0.0	0.73 (0.61–0.89)	0.483	0.0	0.87 (0.76–0.99)	0.533	0.0	0.78 (0.66–0.92)	0.648	0.0	0.87 (0.79–0.95)	0.837	0.0

Notes:

a Number of studies.

b P-value of Q-test for heterogeneity.

c “Y” the total sample size is larger than 1,000; “N” the total sample size is smaller than 1,000.

Abbreviations: HB, hospital-based; OR, odds ratio; PB, population-based.

Figure 2 Forest plots of pancreatic cancer risk associated with NR5A2 rs3790843 G>A polymorphism.

Notes: (A) GA vs GG; (B) GA+AA vs GG; (C) A vs G.
Abbreviation: OR, odds ratio.

Figure 3 Forest plots of pancreatic cancer risk associated with NR5A2 rs3790844 T>C polymorphism.

Notes: (A) CC vs TT; (B) CC vs TT+CT; (C) C vs T. Weights are from random-effects analysis.
Abbreviation: OR, odds ratio.

Figure 4 Forest plots of pancreatic cancer risk associated with NR5A2 rs12029406 C>T polymorphism.

Notes: (A) TT vs CC; (B) TT vs CC+CT; (C) T vs C.
Abbreviation: OR, odds ratio.

Figure 5 Subgroup analysis of ethnicity for NR5A2 rs3790843 G>A polymorphism and pancreatic cancer risk.

Notes: (A) GA vs GG; (B) GA+AA vs GG; (C) A vs G.
Abbreviation: OR, odds ratio.

Figure 6 Subgroup analysis of ethnicity for NR5A2 rs3790844 T>C polymorphism and pancreatic cancer risk.

Notes: (A) CC vs TT; (B) CC vs TT+CT; (C) C vs T. Weights are from random-effects analysis.
Abbreviation: OR, odds ratio.

Table 3 The results of Begg’s and Egger’s tests

Risk model	rs3790843				rs3790844				rs12029406
	Begg’s test		Egger’s test		Begg’s test		Egger’s test		Begg’s test		Egger’s test
	Z	P-value	Z	P-value	Z	P-value	t	P-value	Z	P-value	t	P-value
Heterozygous	0.73	0.462	1.22	0.311	0.38	0.707	0.89	0.426	1.02	0.308	−2.91	0.101
Homozygous	1.22	0.221	2.76	0.070	0.00	1.000	0.92	0.408	0.34	0.734	−0.81	0.501
Dominant	0.24	0.806	0.76	0.503	0.38	0.707	0.36	0.735	1.70	0.089	−3.05	0.093
Recessive	0.73	0.462	1.28	0.292	1.50	0.133	2.35	0.079	0.34	0.734	0.50	0.668
Allele	1.22	0.221	2.45	0.091	0.75	0.452	1.55	0.196	0.34	0.734	−0.99	0.428

Figure S1 Subgroup analysis of type of control source for NR5A2 rs3790843 G>A polymorphism and pancreatic cancer risk.

Notes: (A) GA vs GG; (B) GA+AA vs GG; (C) A vs G.
Abbreviations: HB, hospital-based; OR, odds ratio; PB, population-based.

Figure S2 Subgroup analysis of type of control source for NR5A2 rs3790844 T>C polymorphism and pancreatic cancer risk.

Notes: (A) CC vs TT; (B) CC vs TT+CT; (C) C vs T. Weights are from random-effects analysis.
Abbreviations: HB, hospital-based; OR, odds ratio; PB, population-based.

Figure S3 Subgroup analysis of sample size for NR5A2 rs3790843 G>A polymorphism and pancreatic cancer risk.

Notes: (A) GA vs GG; (B) GA+AA vs GG; (C) A vs G. N, the total sample size is smaller than 1,000; Y, the total sample size is larger than 1,000.
Abbreviation: OR, odds ratio.

Figure S4 Subgroup analysis of sample size for NR5A2 rs3790844 T>C polymorphism and pancreatic cancer risk.

Notes: (A) CC vs TT; (B) CC vs TT+CT; (C) C vs T. N, the total sample size is smaller than 1,000; Y, the total sample size is larger than 1,000. Weights are from random-effects analysis.
Abbreviation: OR, odds ratio.

Figure S5 The sensitivity analysis of pancreatic cancer risk associated with NR5A2 polymorphism.

Notes: (A) Heterozygous model (GA vs GG) for rs3790843 G>A; (B) recessive model (CC vs TT+CT) for rs3790844 T>C; (C) allele model (T vs C) for rs12029406 C>T.

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