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Tumor Biology

, Volume 36, Issue 4, pp 2235–2240 | Cite as

Note of clarification of data in the paper entitled no association between XRCC1 gene Arg194Trp polymorphism and risk of lung cancer: evidence based on an updated cumulative meta-analysis

  • Haiyan Yang
  • Fuye Shao
  • Haiyu Wang
  • Yadong Wang
Editorial
  • 578 Downloads

Keywords

Lung cancer Risk XRCC1 Polymorphism Meta-analysis 

We read with great interest the paper entitled “No association between XRCC1 gene Arg194Trp polymorphism and risk of lung cancer: evidence based on an updated cumulative meta-analysis” published in Tumor Biol. 2014, 35: 5629–5635 [1]. Zhang et al. performed a meta-analysis to explore the association between X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp polymorphism and lung cancer risk on the basis of 25 case-control studies with 8876 cases and 11,210 controls. The authors found that XRCC1 Arg194Trp polymorphism was not associated with lung cancer risk [odds ratio (OR) = 0.97 with 95 % confidence interval (95 %CI): 0.92–1.03 for Trp vs. Arg; OR = 0.92 with 95 %CI: 0.85–0.98 for Arg/Trp vs. Arg/Arg; OR = 1.07 with 95 %CI: 0.92–1.23 for Trp/Trp vs. Arg/Arg; OR = 0.93 with 95 %CI: 0.87–1.00 for Trp/Trp + Arg/Trp vs. Arg/Arg; and OR = 1.08 with 95 %CI: 0.94–1.25 for Trp/Trp vs. Arg/Trp + Arg/Arg]. The cumulative meta-analysis showed that the results maintained the same, while the ORs with 95 % CI were more stable with the accumulation of case-control studies. It is a valuable study.

Nevertheless, careful examination of the data provided by Zhang et al. [1] (shown in Table 1 in their original text) revealed two key issues that are worth noticing. Firstly, one overlapping paper [2] was not properly excluded from Zhang et al.’s study [1]. Secondly, the data reported by Zhang et al. [1] for the study by Wang et al. [3] do not seem in line with the data provided by Wang et al. [3] in their original publication. The numbers reported by Wang et al. [3] (shown in Table 1 in Wang et al.’s original paper) for Arg/Arg, Arg/Trp, and Trp/Trp, in cases and controls, are 89, 80, and 40 and 138, 90, and 28, respectively. Interestingly enough, after carefully examining the data reported by Zhang et al. [1], the numbers are 105, 83, and 21 in cases and 137, 96, and 23 in controls, respectively (supporting information). Therefore, the conclusions by Zhang et al. [1] are not entirely reliable. It is required to clarify the association between XRCC1 Arg194Trp polymorphism and lung cancer risk. We reassessed this association by performing a meta-analysis on the basis of a total of 30 studies with 9508 cases and 11,845 controls, which may provide comprehensive evidence for the association of XRCC1 Arg194Trp polymorphism with lung cancer risk.

Table 1 listed the general information of selected studies. Table 2 listed the summary odds ratios of the association between XRCC1 Arg194Trp polymorphism and lung cancer risk. Overall, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 194 Trp/Trp genotype (OR = 1.26, 95 %CI: 1.10–1.45) compared with Arg/Arg genotype carriers in total population (Fig. 1a). We did not observe any association of Arg/Trp and Trp/Trp + Arg/Trp polymorphisms with lung cancer risk (OR = 0.96, 95 %CI: 0.86–1.08 for Arg/Trp vs. Arg/Arg and OR = 1.01, 95 %CI: 0.90–1.14 for Trp/Trp + Arg/Trp vs. Arg/Arg, respectively) (Fig. 1b, c). The cumulative meta-analysis accumulated the studies in the light of publication year and showed that there was still a significant association between XRCC1 codon 194 Trp/Trp polymorphism and lung cancer risk, the cumulative odds ratio was 1.26 with 95 %CI: 1.09–1.45 (Fig. 2). Limiting the analysis to the studies with controls in agreement with Hardy-Weinberg equilibrium (HWE), we observed an increased risk of lung cancer among subjects carrying Trp/Trp genotype, compared with Arg/Arg genotype (OR = 1.17, 95 %CI: 1.01–1.36) (Table 2). When the subgroup analysis was performed by ethnicity, we observed an increased lung cancer risk among subjects carrying XRCC1 codon 194 Trp/Trp genotype, compared with Arg/Arg genotype carries in Asians (OR = 1.28, 95 %CI: 1.11–1.47), but we observed a decreased lung cancer risk among subjects carrying XRCC1 codon 194 Arg/Trp and Arg/Trp + Trp/Trp genotypes compared with Arg/Arg genotype carries in Caucasians (OR = 0.85, 95 %CI: 0.73–0.99 for Arg/Trp vs. Arg/Arg and OR = 0.86, 95 %CI: 0.76–0.97 for Arg/Trp + Trp/Trp vs. Arg/Arg, respectively) (Table 2). In subgroup analysis by source of control, we observed an increased risk of XRCC1 codon Arg194Trp polymorphism for lung cancer in the genetic model of Trp/Trp vs. Arg/Arg based on population-based control and hospital-based control (OR = 1.28, 95%CI: 1.03–1.59 and OR = 1.25, 95 %CI: 1.05–1.49) (Table 2). A decreased lung cancer risk was observed among smokers carrying XRCC1 codon 194 Arg/Trp + Trp/Trp genotype compared with Arg/Arg genotype carries (OR = 0.83, 95 %CI: 0.71–0.98) when stratified by smoking status (Table 2). We did not observe any association between XRCC1 Arg194Trp polymorphism and lung cancer risk in additional subgroup analyses (Table 2).
Table 1

Characteristics of selected papers

Author

Year

Country

Ethnicity

Source of control

Number of case

Number of control

HWE

Buch Shama [6]

2012

USA

Caucasian

HB

720

928

0.015858

Chan Eunice [7]

2005

China

Asian

HB

75

162

0.745951

Chang Jeffrey-A [8]

2009

USA

African

PB

255

280

0.976205

Chang Jeffrey-C [8]

2009

USA

Caucasian

PB

113

299

0.073084

Chen Senqing [9]

2002

China

Asian

PB

103

102

0.546278

David-Beabes-A [10]

2001

USA

African

PB

154

243

0.736731

David-Beabes-C [10]

2001

USA

Caucasian

PB

180

461

0.181632

De Ruyck Kim [11]

2007

Belgium

Caucasian

HB

110

110

0.379774

Du Yong [12]

2012

China

Asian

HB

100

100

0.000012

Du Yong [5]

2014

China

Asian

HB

120

120

0.000009

Guo Shujie [13]

2013

China

Asian

HB

684

602

0.526784

Hao B. [14]

2006

China

Asian

PB

1024

1118

0.701669

Hu Zhibin [15]

2005

China

Asian

HB

710

710

0.556829

Hung Rayjean [16]

2005

Mixed

Caucasian

HB

2147

2132

0.926867

Improta Giuseppina [17]

2008

Italy

Caucasian

HB

94

121

0.405911

Janik Justyna [18]

2011

Poland

Caucasian

HB

88

79

0.548137

Li Mingchuan [19]

2008

China

Asian

HB

350

350

0.803017

Matullo G. [20]

2006

Mixed

Caucasian

PB

116

1094

0.170586

Pachouri Suparna [21]

2007

India

Asian

PB

103

122

0.042833

Ratnasinghe Duminda [22]

2001

China

Asian

PB

108

210

0.182984

Schneider Joachim [23]

2005

German

Caucasian

HB

446

622

0.811054

Shen Min [24]

2005

China

Asian

HB

118

112

0.614295

Song Yahui [4]

2004

China

Asian

HB

100

65

0.797994

Su Jia [25]

2008

China

Asian

PB

396

465

0.126621

Tanaka Yugo [26]

2010

Japan

Asian

PB

50

50

0.237879

Wang Na [3]

2012

China

Asian

HB

209

256

0.027626

Yin Jiaoyong [27]

2007

China

Asian

HB

241

249

0.570251

Yu Hongping [28]

2006

China

Asian

HB

104

121

0.043211

Zhang Wenjuan [29]

2005

China

Asian

HB

149

157

0.356342

Zienolddiny Shanbeh [30]

2006

Norway

Caucasian

PB

336

405

0.249941

HB hospital-based control, PB population-based control, HWE Hardy-Weinberg equilibrium

Table 2

Summary of odds ratios for the relationship of XRCC1 Arg194Trp polymorphism with lung cancer risk

Genotype

Case/control

Heterogeneity test

Summary OR (95 % CI)

Hypothesis test

df

Begg's test

Egger's test

Q

P

Z

P

Z

P

t

P

Total

 Trp/Trp vs. Arg/Arg

7124/8969

39.17

0.05

1.26 (1.10–1.45)

3.34

0.0008

26

0.57

0.568

0.51

0.613

 Arg/Trp vs. Arg/Arg

8981/11,378

59.95

0.0006

0.96 (0.86–1.08)

0.70

0.49

29

0.21

0.830

0.43

0.672

 Trp/Trp + Arg/Trp vs. Arg/Arg

9503/11,845

72.47

<0.0001

1.01 (0.90–1.14)

0.22

0.82

29

0.75

0.454

0.80

0.430

Stratification by HWE

Yes

 Trp/Trp vs. Arg/Arg

6018/7630

29.09

0.09

1.17 (1.01–1.36)

2.09

0.04

20

0.00

1.000

0.51

0.614

 Arg/Trp vs. Arg/Arg

7731/9812

40.00

0.02

0.94 (0.84–1.05)

1.08

0.28

23

0.62

0.535

0.07

0.945

 Trp/Trp + Arg/Trp vs. Arg/Arg

8147/10,198

43.74

0.0006

0.98 (0.87–1.10)

0.38

0.71

23

0.07

0.941

0.39

0.700

Stratification by ethnicity

Caucasian

 Trp/Trp vs. Arg/Arg

3884/5461

13.56

0.06

1.13 (0.69–1.87)

0.49

0.63

7

0.00

1.000

0.20

0.851

 Arg/Trp vs. Arg/Arg

4322/6216

10.55

0.31

0.85 (0.73–0.99)

2.10

0.04

9

0.18

0.858

0.17

0.872

 Trp/Trp + Arg/Trp vs. Arg/Arg

4350/6251

12.78

0.07

0.86 (0.76–0.97)

2.41

0.02

9

0.72

0.474

0.35

0.736

Asian

 Trp/Trp vs. Arg/Arg

2875/3052

24.76

0.07

1.28 (1.11–1.47)

3.35

0.0008

16

0.04

0.967

1.18

0.258

 Arg/Trp vs. Arg/Arg

4252/4642

38.29

0.002

1.04 (0.90–1.20)

0.47

0.64

17

0.76

0.449

1.11

0.282

 Trp/Trp + Arg/Trp vs. Arg/Arg

4744/5071

46.91

0.0001

1.11 (0.95–1.29)

1.31

0.19

17

1.14

0.256

1.35

0.196

Stratification by source of control

Population-based study

 Trp/Trp vs. Arg/Arg

2116/3648

14.23

0.16

1.28 (1.03–1.59)

2.22

0.03

10

0.36

0.721

0.43

0.678

 Arg/Trp vs. Arg/Arg

2739/4657

10.98

0.45

0.96 (0.86–1.08)

0.61

0.54

11

0.75

0.451

0.94

0.367

 Trp/Trp + Arg/Trp vs. Arg/Arg

2938/4849

12.70

0.31

1.00 (0.90–1.12)

0.08

0.94

11

0.07

0.945

0.76

0.465

Hospital-based study

 Trp/Trp vs. Arg/Arg

5008/5321

24.85

0.05

1.25 (1.05–1.49)

2.50

0.01

15

0.77

0.443

0.29

0.776

 Arg/Trp vs. Arg/Arg

6242/6721

48.95

<0.0001

0.98 (0.83–1.16)

0.24

0.81

17

0.45

0.649

0.90

0.381

 Trp/Trp + Arg/Trp vs. Arg/Arg

6565/6996

56.67

<0.00001

1.04 (0.88–1.25)

0.49

0.63

17

1.21

0.225

1.26

0.226

Stratified by smoking status

Smoker

 Trp/Trp + Arg/Trp vs. Arg/Arg

2869/2427

5.43

0.37

0.83 (0.71–0.98)

2.25

0.02

5

0.75

0.452

0.34

0.751

HWE Hardy-Weinberg equilibrium

Fig. 1

Forest plots for the association of XRCC1 Arg194Trp polymorphism with lung cancer risk (a Trp/Trp vs. Arg/Arg, b Arg/Trp vs. Arg/Arg, and c: Arg/Trp + Trp/Trp vs. Arg/Arg)

Fig. 2

Forest plot for cumulative meta-analysis based on Trp/Trp vs. Arg/Arg

The shape of funnel plots seemed to be approximately symmetrical (Fig. 3a–c). Both Egger’s test and Begg’s test results suggested no evidence of publication biases existed in this meta-analysis (Table 2).
Fig. 3

Funnel plots for the association of XRCC1 Arg194Trp polymorphism with lung cancer risk (a Trp/Trp vs. Arg/Arg, b Arg/Trp vs. Arg/Arg, and c Arg/Trp + Trp/Trp vs. Arg/Arg)

Sensitivity analysis was performed to evaluate the root of heterogeneity. The combined estimates were not altered when the studies were lack of heterogeneity for Arg/Trp vs. Arg/Arg and Trp/Trp + Arg/Trp vs. Arg/Arg polymorphisms among total population by deleting Song et al.’s study [4], Du et al.’s study [5], and Buch et al.’s study [6] (data not shown).

In conclusion, the findings of Zhang et al.’s study [1] should be interpreted with caution. To draw a definitive conclusion, further well-designed studies with large sample size are still required to assess the association of XRCC1 Arg194Trp polymorphism with lung cancer risk. We hope that our remarks will contribute to a more accurate elaboration and substantiation of the results provided by Zhang et al. [1].

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Haiyan Yang
    • 1
  • Fuye Shao
    • 1
  • Haiyu Wang
    • 2
  • Yadong Wang
    • 2
  1. 1.Department of Epidemiology, School of Public HealthZhengzhou UniversityZhengzhouChina
  2. 2.Department of ToxicologyHenan Center for Disease Control and PreventionZhengzhouChina

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