Association of estrogen receptor α PvuII and XbaI polymorphisms with prostate cancer susceptibility and risk stratification: a meta-analysis from case-control studies

Figures & data

Figure 1 Flow of information through different phases of the present meta-analysis.

Abbreviation: SNP, single nucleotide polymorphisms.

Table 1 Characteristics and methodological quality of included studies

Study	Ethnicity	Country	SOC	Sample	Genotyping method	Participants		HWE	STREGA score
						Case	Control
PvuII (rs2234693 T>C) (n=18)
Modugno et al,^Citation10 2001	Caucasian	America	PB	Blood	PCR	81	233	Y	30
Suzuki et al,^Citation11 2003	Asian	Japan	PB	Blood	PCR	101	114	Y	31
Tanaka et al,^Citation12 2003	Asian	Japan	PB	Tissue	PCR	115	200	Y	29
Fukatsu et al,^Citation13 2004	Asian	Japan	Mixed	Tissue	PCR	116	238	Y	31
Hernández et al,^Citation14 2006	Mixed	NA	Mixed	Blood	TaqMan	598	1,098	Y	31
Low et al,^Citation15 2006	Caucasian	Britain	NA	Urine	TaqMan	75	158	Y	32
Berndt et al,^Citation16 2007	Caucasian	NA	PB	Blood	TaqMan	470	603	Y	31
Kjaergaard et al,^Citation17 2007	Caucasian	Denmark	HB	NA	PCR	116	4,005	Y	36
Onsory et al,^Citation18 2008	Asian	India	HB	Tissue	PCR	100	100	Y	32
Sobti et al,^Citation19 2008	Asian	India	HB	Blood	PCR	157	170	Y	31
Gupta et al,^Citation20 2010	Asian	India	HB	Blood	PCR	157	170	Y	31
Balistreri et al,^Citation21 2011	Caucasian	Sicily	NA	Tissue	TaqMan	50	47	Y	32
Sissung et al,^Citation22 2011	Caucasian	America	PB	Blood	PCR	128	126	Y	32
Szendroi et al,^Citation23 2011	Caucasian	Hungary	PB	Blood	PCR	194	103	Y	31
Safarinejad et al,^Citation24 2012	Asian	Iran	NA	Blood	PCR	162	324	Y	32
Jurecekova et al,^Citation25 2013	Caucasian	Slovakia	PB	Blood	PCR	311	256	Y	33
Pazarbasi et al,^Citation26 2013	Asian	Turkey	PB	Blood	PCR	34	27	N	32
Lu et al,^Citation27 2015	Asian	Japan	PB	Blood	PCR	352	352	Y	30
XbaI (rs9340799 A>G) (n=11)
Modugno et al,^Citation10 2001	Caucasian	America	PB	Blood	PCR	82	237	Y	30
Suzuki et al,^Citation11 2003	Asian	Japan	PB	Blood	PCR	101	114	N	31
Fukatsu et al,^Citation13 2004	Asian	Japan	Mixed	Tissue	PCR	117	242	Y	31
Hernández et al,^Citation14 2006	Mixed	NA	Mixed	Blood	TaqMan	598	1,098	Y	31
Gupta et al,^Citation20 2010	Asian	India	HB	Blood	PCR	157	170	Y	31
Balistreri et al,^Citation21 2011	Caucasian	Sicily	NA	Tissue	TaqMan	50	47	Y	32
Sissung et al,^Citation22 2011	Caucasian	America	PB	Blood	PCR	129	127	Y	32
Szendroi et al,^Citation23 2011	Caucasian	Hungary	PB	Blood	PCR	205	101	Y	31
Safarinejad et al,^Citation24 2012	Asian	Iran	NA	Blood	PCR	162	324	N	32
Jurecekova et al,^Citation25 2013	Caucasian	Slovak	PB	Blood	PCR	311	256	Y	33
Pazarbasi et al,^Citation26 2013	Asian	Turkish	PB	Blood	PCR	34	28	Y	32

Notes: The study also used blood as testing sample. All cases came from hospital-based populations.

Abbreviations: SOC, source of controls; HWE, Hardy–Weinberg equilibrium (Y, HWE in controls; N, HWE out of controls); STREGA, Strengthening the Reporting of Genetic Association Studies; PB, population-based; PCR, polymerase chain reaction; NA, nonapplicable; HB, hospital-based.

Table 2 Meta-analysis findings on the association between ERα PvuII (rs2234693 T>C) polymorphism and prostate cancer risk

Subgroup (size)	I^2		OR (95% CI)	P-value
Allele model (C vs T)
Overall (n=20)	57.1%		1.16 (1.04–1.29)	<0.01
Caucasian (n=11)	37.8%		1.12 (1.03–1.21)	<0.01
Asian (n=8)	74.6%		1.09 (0.85–1.39)	0.50
HWE in controls (n=19)	56.7%		1.17 (1.05–1.30)	<0.01
Dominant model (TC + CC vs TT)
Overall (n=20)	55.2%		1.24 (1.06–1.46)	0.01
Caucasian (n=11)	38.0%		1.19 (1.05–1.35)	<0.01
Asian (n=8)	73.3%		1.17 (0.79–1.73)	0.42
HWE in controls (n=19)	57.1%		1.25 (1.06–1.48)	<0.01
Recessive model (CC vs TT + TC)
Overall (n=20)	38.1%		1.16 (1.04–1.30)	<0.01
Caucasian (n=11)	4.4%		1.13 (1.03–1.29)	0.04
Asian (n=8)	62.5%		1.17 (0.81–1.70)	0.13
HWE in controls (n=19)	33.1%		1.18 (1.05–1.31)	<0.01
Homozygous model (CC vs TT)
Overall (n=20)	58.6%		1.37 (1.09–1.72)	<0.01
Caucasian (n=11)	29.5%		1.25 (1.06–1.46)	0.01
Asian (n=8)	77.2%		1.31 (0.73–2.33)	0.35
HWE in controls (n=19)	58.2%		1.41 (1.12–1.77)	<0.01
Heterozygous model (CC vs TC)
Overall (n=20)	14.7%		1.11 (0.99–1.25)	0.07
Caucasian (n=11)	0.0%		1.07 (0.93–1.23)	0.29
Asian (n=8)	44.4%		1.16 (0.93–1.45)	0.17
HWE in controls (n=19)	3.5%		1.12 (1.00–1.26)	0.05

Notes: If I²<50%, the fixed effects model was used. Otherwise, the random effects model was used.

Abbreviations: ERα, estrogen receptor α; OR, crude odds ratio; CI, confidence interval; HWE, Hardy–Weinberg equilibrium.

Table 3 Subgroup analysis by Gleason score of the association between ERα PvuII (rs2234693 T>C) polymorphism and prostate cancer risk under the allele model (T vs C)

Study (n=2)	Ethnicity	Gleason score					OR (95% CI)	Weight (%)
		≥7		<7
		C	T	C	T
Safarinejad et al,^Citation24 2012	Asian	150	58	90	58		1.67 (1.06–2.60)	41.09
Jurecekova et al,^Citation25 2013	Caucasian	299	133	98	90		2.07 (1.45–2.93)	58.91
Overall (I^2=0.0%)							1.90 (1.44–2.50)	100

Note: I²<50%, the fixed effects model was used.

Abbreviations: ERα, estrogen receptor α; OR, crude odds ratio; CI, confidence interval.

Figure 2 Begg’s funnel plot for the publication bias test of the meta-analysis.

Notes: Each point represents a separate study for the indicated association. Horizontal line represents size of effect. (A) ERα PvuII polymorphism (t=1.07, P=0.30) and (B) ERα XbaI polymorphism (t=0.66, P=0.52).
Abbreviations: ERα, estrogen receptor α; OR, crude odds ratio; SE, standard error.

Table 4 Meta-analysis findings on the association between ERα XbaI (rs9340799 A>G) polymorphism and prostate cancer risk

Subgroup (size)	I^2		OR (95% CI)	P-value
Allele model (G vs A)
Overall (n=13)	56.5%		1.23 (1.06–1.43)	<0.01
Caucasian (n=7)	64.5%		1.31 (1.07–1.61)	<0.01
Asian (n=5)	54.5%		1.05 (0.80–1.37)	0.70
HWE in controls (n=11)	56.6%		1.25 (1.06–1.47)	<0.01
Dominant model (AG + GG vs AA)
Overall (n=13)	59.2%		1.38 (1.11–1.72)	<0.01
Caucasian (n=7)	65.5%		1.43 (1.07–1.92)	0.01
Asian (n=5)	58.1%		1.21 (0.82–1.79)	0.31
HWE in controls (n=11)	53.1%		1.37 (1.11–1.70)	<0.01
Recessive model (GG vs AA + AG)
Overall (n=13)	6.0%		1.24 (1.03–1.49)	0.03
Caucasian (n=7)	0.0%		1.36 (1.09–1.69)	<0.01
Asian (n=5)	26.1%		1.00 (0.71–1.42)	0.79
HWE in controls (n=11)	10.5%		1.27 (1.04–1.55)	0.01
Homozygous model (GG vs AA)
Overall (n=13)	43.5%		1.44 (1.17–1.76)	<0.01
Caucasian (n=7)	45.1%		1.48 (1.17–1.88)	<0.01
Asian (n=5)	59.6%		1.05 (0.52–2.09)	0.21
HWE in controls (n=11)	38.0%		1.40 (1.13–1.74)	<0.01
Heterozygous model (GG vs AG)
Overall (n=13)	0.0%		1.11 (0.92–1.35)	0.25
Caucasian (n=7)	0.0%		1.24 (0.98–1.57)	0.06
Asian (n=5)	0.0%		0.90 (0.62–1.29)	0.57
HWE in controls (n=11)	0.0%		1.15 (0.92–1.42)	0.20

Notes: If I²<50%, the fixed effects model was used. Otherwise, the random effects model was used.

Abbreviations: ERα, estrogen receptor α; OR, crude odds ratio; CI, confidence interval; HWE, Hardy–Weinberg equilibrium.

ModugnoFWeissfeldJLTrumpDLAllelic variants of aromatase and the androgen and estrogen receptors: toward a multigenic model of prostate cancer riskClin Cancer Res20017103092309611595700

 PubMedGoogle Scholar

SuzukiKNakazatoHMatsuiHGenetic polymorphisms of estrogen receptor alpha, CYP19, catechol-O-methyltransferase are associated with familial prostate carcinoma risk in a Japanese populationCancer20039871411141614508827

 PubMed Web of Science ®Google Scholar

TanakaYSasakiMKaneuchiMShiinaHIgawaMDahiyaRPolymorphisms of estrogen receptor alpha in prostate cancerMol Carcinog200337420220812891629

 PubMedGoogle Scholar

FukatsuTHirokawaYArakiTGenetic polymorphisms of hormone-related genes and prostate cancer risk in the Japanese populationAnticancer Res20042442431243715330195

 PubMed Web of Science ®Google Scholar

HernándezJBalicIJohnson-PaisTLAssociation between an eestrogen receptor alpha gene polymorphism and the risk of prostate cancer in black menJ Urol2006175252352716406987

 PubMedGoogle Scholar

LowYLTaylorJIGracePBPhytoestrogen exposure, polymorphisms in COMT, CYP19, ESR1, and SHBG genes, and their associations with prostate cancer riskNutr Cancer2006561313917176215

 PubMed Web of Science ®Google Scholar

BerndtSIChatterjeeNHuangWYVariant in sex hormone-binding globulin gene and the risk of prostate cancerCancer Epidemiol Biomarkers Prev200716116516817220347

 PubMedGoogle Scholar

KjaergaardADEllervikCTybjaerg-HansenAEstrogen receptor alpha polymorphism and risk of cardiovascular disease, cancer, and hip fracture: cross-sectional, cohort, and case-control studies and a meta-analysisCirculation2007115786187117309937

 PubMedGoogle Scholar

OnsoryKSobtiRCAl-BadranAIHormone receptor-related gene polymorphisms and prostate cancer risk in North Indian populationMol Cell Biochem20083141–2253518483761

 PubMed Web of Science ®Google Scholar

SobtiRCGuptaLSinghSKSethAKaurPThakurHRole of hormonal genes and risk of prostate cancer: gene-gene interactions in a North Indian populationCancer Genet Cytogenet20081852788518722876

 PubMedGoogle Scholar

GuptaLThakurHSobtiRCSethASinghSKRole of genetic polymorphism of estrogen receptor-alpha gene and risk of prostate cancer in north Indian populationMol Cell Biochem20103351–225526119904497

 PubMedGoogle Scholar

BalistreriCRCarusoCCarrubaGMiceliVCandoreGGenotyping of sex hormone-related pathways in benign and malignant human prostate tissues: data of a preliminary studyOMICS201115636937421348640

 PubMed Web of Science ®Google Scholar

SissungTMDanesiRKirklandCTEstrogen receptor alpha and aromatase polymorphisms affect risk, prognosis, and therapeutic outcome in men with castration-resistant prostate cancer treated with docetaxel-based therapyJ Clin Endocrinol Metab2011962E368E37221106711

 PubMedGoogle Scholar

SzendroiASpeerGTabakAThe role of vitamin D, estrogen, calcium sensing receptor genotypes and serum calcium in the pathogenesis of prostate cancerCan J Urol20111835710571621703046

 PubMed Web of Science ®Google Scholar

SafarinejadMRSafarinejadSShafieiNSafarinejadSEstrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes polymorphism in prostate cancer: evidence for association with risk and histopathological tumor characteristics in Iranian menMol Carcinog201251Suppl 1E104E11722228197

 PubMedGoogle Scholar

JurecekovaJSivonovaMKEvinovaAKlimentJDobrotaDThe association between estrogen receptor alpha polymorphisms and the risk of prostate cancer in Slovak populationMol Cell Biochem20133811–220120723737135

 PubMedGoogle Scholar

PazarbasiAYilmazMBAlptekinDGenetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinomaIndian J Hum Genet201319440841124497704

 PubMedGoogle Scholar

LuXYamanoYTakahashiHAssociations between estrogen receptor genetic polymorphisms, smoking status, and prostate cancer risk: a case-control study in Japanese menEnviron Health Prev Med201520533233726251204

 PubMedGoogle Scholar