Association between polymorphisms in DNA repair gene XRCC1 and non-melanoma skin cancer risk: a meta-analysis

Figures & data

Figure 1 Selection process of all eligible articles of this meta-analysis.

Table 1 The detailed characteristics of all studies included in this meta-analysis

Author	Year	Country (ethnicity)	Mean age (years)		Sample size		Tumor types	Genotyping method	HWE in controls
			Cases	Controls	Cases	Controls
Nelson et al^Citation29	2002	UK (Caucasians)	–	–	745	431	BCC + SCC	PCR-RFLP	0.185
Yin et al^Citation30	2002	Denmark (Caucasians)	20–60	20–60	63	97	BCC	SNaPshot	0.774
Yin et al^Citation31	2003	Denmark (Caucasians)	<50	<50	20	20	BCC	PCR-RFLP	0.983
Han et al^Citation32	2005	USA (Caucasians)	64.7	64.5	586	874	BCC + SCC	Sequencing	0.161
Festa et al^Citation33	2005	Sweden/Finland (Caucasians)	–	–	197	548	BCC	PCR-RFLP	0.973
Thirumaran et al^Citation34	2006	Sweden (Caucasians)	63.5±11.7	60.0±11.8	529	533	BCC	Sequencing	0.838
Kang et al^Citation35	2007	Korea (Asian)	68.98±12.6	46.42±16.6	212	207	BCC + SCC	PCR-RFLP	0.673
Chiyomaru et al^Citation36	2012	Japan (Asian)	72.9±12.2	66.1±13.7	103	93	BD + BCC + SCC	PCR-RFLP	0.097
Surdu et al^Citation37	2014	Germany (Caucasians)	30–79	30–79	618	527	BCC + SCC	Sequencing	0.838
Hsu et al^Citation38	2015	China Taiwan (Asian)	56.13±6.87	54.38±6.26	70	210	BCC + SCC + BD	PCR-RFLP	0.156

Note: The data are presented as mean values ± standard deviation.

Abbreviations: –, not available; BCC, basal-cell skin cancer; SCC, squamous-cell skin cancer; BD, Bowen’s diseases; PCR-RFLP, polymerase chain reaction-restriction fragment length polymorphism; HWE, Hardy–Weinberg equilibrium.

Figure 2 Forest plot of the association between XRCC1 Arg399Gln polymorphism and non-melanoma skin cancer risk under allelic model.

Abbreviation: NMSC, non-melanoma skin cancer.

Table 2 Meta-analysis and stratified analyses of Arg399Gln, Arg194Trp, and Arg280His in the coding region of XRCC1 gene with NMSC risk under each genetic model

SNPs	Group	N	Comparisons	Test of association		Test of heterogeneity
				OR (95% CI)	P-value	I^2 (%)	Ph	Model
Arg399Gln		10	Gln vs Arg	0.97 (0.90–1.05)	0.42	26	0.21	F
			Gln/Gln vs Arg/Arg	0.90 (0.77–1.06)	0.20	22	0.24	F
			Gln/Arg vs Arg/Arg	1.02 (0.92–1.14)	0.69	0	0.46	F
			Gln/Gln + Gln/Arg vs Arg/Arg	0.99 (0.90–1.10)	0.89	5	0.40	F
			Gln/Gln vs Gln/Arg + Arg/Arg	0.90 (0.77–1.04)	0.16	28	0.18	F
	Asian	3	Gln vs Arg	1.04 (0.70–1.55)	0.85	70	0.04	R
			Gln/Gln vs Arg/Arg	0.94 (0.43–2.05)	0.88	61	0.07	R
			Gln/Arg vs Arg/Arg	1.39 (1.04–1.87)	0.03	0	0.70	F
			Gln/Gln + Gln/Arg vs Arg/Arg	1.26 (0.96–1.66)	0.10	38	0.20	F
			Gln/Gln vs Gln/Arg + Arg/Arg	0.83 (0.41–1.70)	0.61	57	0.10	R
	Caucasians	7	Gln vs Arg	0.95 (0.88–1.03)	0.24	0	0.67	F
			Gln/Gln vs Arg/Arg	0.90 (0.76–1.07)	0.22	5	0.39	F
			Gln/Arg vs Arg/Arg	0.98 (0.87–1.09)	0.67	0	0.78	F
			Gln/Gln + Gln/Arg vs Arg/Arg	0.96 (0.86–1.07)	0.42	0	0.82	F
			Gln/Gln vs Gln/Arg + Arg/Arg	0.91 (0.77–1.06)	0.23	23	0.25	F
	BCC	9	Gln vs Arg	0.97 (0.90–1.06)	0.51	40	0.10	F
			Gln/Gln vs Arg/Arg	0.89 (0.74–1.06)	0.20	2	0.42	F
			Gln/Arg vs Arg/Arg	1.04 (0.92–1.17)	0.52	45	0.07	F
			Gln/Gln + Gln/Arg vs Arg/Arg	1.00 (0.90–1.12)	0.94	46	0.06	F
			Gln/Gln vs Gln/Arg + Arg/Arg	0.89 (0.72–1.09)	0.24	20	0.27	F
	SCC	5	Gln vs Arg	0.99 (0.78–1.25)	0.92	63	0.03	R
			Gln/Gln vs Arg/Arg	0.99 (0.56–1.76)	0.98	71	0.008	R
			Gln/Arg vs Arg/Arg	0.99 (0.82–1.19)	0.88	0	0.58	F
			Gln/Gln + Gln/Arg vs Arg/Arg	0.95 (0.80–1.13)	0.57	19	0.30	F
			Gln/Gln vs Gln/Arg + Arg/Arg	0.97 (0.57–1.64)	0.90	70	0.01	R
Arg194Trp		4	Trp vs Arg	0.98 (0.82–1.19)	0.86	46	0.13	F
			Trp/Trp vs Arg/Arg	0.72 (0.43–1.22)	0.22	0	0.88	F
			Trp/Arg vs Arg/Arg	1.10 (0.72–1.70)	0.65	60	0.06	R
			Trp/Trp + Trp/Arg vs Arg/Arg	1.03 (0.69–1.54)	0.87	58	0.07	R
			Trp/Trp vs Trp/Arg + Arg/Arg	0.72 (0.44–1.20)	0.21	0	0.97	F
	Asian	2	Trp vs Arg	0.91 (0.61–1.36)	0.64	58	0.12	R
			Trp/Trp vs Arg/Arg	0.74 (0.41–1.31)	0.30	0	0.53	F
			Trp/Arg vs Arg/Arg	1.06 (0.45–2.51)	0.90	82	0.02	R
			Trp/Trp + Trp/Arg vs Arg/Arg	0.97 (0.47–2.01)	0.94	78	0.03	R
			Trp/Trp vs Trp/Arg + Arg/Arg	0.74 (0.43–1.29)	0.29	0	0.98	F
	Caucasians	2	Trp vs Arg	1.17 (0.87–1.56)	0.30	0	0.34	F
			Trp/Trp vs Arg/Arg	0.66 (0.18–2.35)	0.52	0	0.62	F
			Trp/Arg vs Arg/Arg	1.27 (0.92–1.74)	0.14	0	0.73	F
			Trp/Trp + Trp/Arg vs Arg/Arg	1.22 (0.90–1.67)	0.20	0	0.50	F
			Trp/Trp vs Trp/Arg + Arg/Arg	0.64 (0.18–2.29)	0.50	0	0.64	F
	BCC	4	Trp vs Arg	1.02 (0.81–1.29)	0.84	0	0.59	F
			Trp/Trp vs Arg/Arg	0.97 (0.53–1.77)	0.92	0	0.80	F
			Trp/Arg vs Arg/Arg	1.06 (0.80–1.41)	0.68	0	0.49	F
			Trp/Trp + Trp/Arg vs Arg/Arg	1.05 (0.80–1.38)	0.73	0	0.53	F
			Trp/Trp vs Trp/Arg + Arg/Arg	1.25 (0.70–2.25)	0.46	0	0.74	F
	SCC	3	Trp vs Arg	0.91 (0.55–1.51)	0.71	73	0.03	R
			Trp/Trp vs Arg/Arg	0.38 (0.16–0.92)	0.03	0	0.90	F
			Trp/Arg vs Arg/Arg	1.11 (0.52–2.38)	0.78	82	0.004	R
			Trp/Trp + Trp/Arg vs Arg/Arg	0.99 (0.49–2.00)	0.98	80	0.007	R
			Trp/Trp vs Trp/Arg + Arg/Arg	0.42 (0.18–1.00)	0.05	0		F
Arg280His		2	His vs Arg	0.88 (0.38–2.05)	0.78	74	0.05	R
			His/His vs Arg/Arg	0.87 (0.21–3.50)	0.84	0	0.34	F
			His/Arg vs Arg/Arg	0.97 (0.48–1.95)	0.93	58	0.12	R
			His/His + His/Arg vs Arg/Arg	0.92 (0.41–2.07)	0.84	69	0.07	R
			His/His vs His/Arg + Arg/Arg	0.87 (0.21–3.53)	0.84	0	0.38	F

Abbreviations: NMSC, non-melanoma skin cancer; SNP, single nucleotide polymorphism; N, number of included studies; OR, odds ratio; CI, confidence interval; F, fixed-effect model; R, random-effect model; BCC, basal-cell skin cancer; SCC, squamous-cell skin cancer; Ph, P-value of heterogeneity.

Figure 3 Forest plot obtained by subgroup analysis based on ethnicity showing the association between XRCC1 Arg399Gln polymorphism and non-melanoma skin cancer risk under heterogeneous model in Asian populations.

Abbreviation: NMSC, non-melanoma skin cancer.

Figure 4 Forest plot obtained by subgroup analysis based on tumor types showing the association between XRCC1 Arg194Trp polymorphism and squamous-cell skin cancer risk under homogeneous model.

Abbreviation: SCC, squamous-cell skin cancer.

Figure 5 Funnel plot showing XRCC1 Arg399Gln polymorphism in non-melanoma skin cancer risk under allelic model.

Abbreviations: OR, odds ratio; SE, standard error.

NelsonHHKelseyKTMottLAKaragasMRThe XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interactionCancer Res200262115215511782372

 PubMed Web of Science ®Google Scholar

YinJRockenbauerEHedayatiMMultiple single nucleotide polymorphisms on human chromosome 19q13.2-3 associate with risk of Basal cell carcinomaCancer Epidemiol Biomarkers Prev200211111449145312433725

 PubMedGoogle Scholar

YinJVogelUGerdesLUDybdahlMBolundLNexoBATwelve single nucleotide polymorphisms on chromosome 19q13.2-13.3: linkage disequilibria and associations with basal cell carcinoma in Danish psoriatic patientsBiochem Genet2003411–2273712645871

 PubMedGoogle Scholar

HanJColditzGALiuJSHunterDJGenetic variation in XPD, sun exposure, and risk of skin cancerCancer Epidemiol Biomarkers Prev20051461539154415941969

 PubMedGoogle Scholar

FestaFKumarRSanyalSBasal cell carcinoma and variants in genes coding for immune response, DNA repair, folate and iron metabolismMutat Res20055741–210511115914210

 PubMedGoogle Scholar

ThirumaranRKBermejoJLRudnaiPSingle nucleotide polymorphisms in DNA repair genes and basal cell carcinoma of skinCarcinogenesis20062781676168116501254

 PubMedGoogle Scholar

KangSYLeeKGLeeWPolymorphisms in the DNA repair gene XRCC1 associated with basal cell carcinoma and squamous cell carcinoma of the skin in a Korean populationCancer Sci200798571672017355263

 PubMed Web of Science ®Google Scholar

ChiyomaruKNaganoTNishigoriCXRCC1 Arg194Trp polymorphism, risk of nonmelanoma skin cancer and extramammary Paget’s disease in a Japanese populationArch Dermatol Res2012304536337022639094

 PubMedGoogle Scholar

SurduSFitzgeraldEFBloomMSPolymorphisms in DNA repair genes XRCC1 and XRCC3, occupational exposure to arsenic and sunlight, and the risk of non-melanoma skin cancer in a European case-control studyEnviron Res201413438238925218703

 PubMedGoogle Scholar

HsuLIWuMMWangYHAssociation of environmental arsenic exposure, genetic polymorphisms of susceptible genes, and skin cancers in TaiwanBioMed Res Int2015201589257926295053

 PubMedGoogle Scholar