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The Effect of XPD Polymorphisms on Digestive Tract Cancers Risk: A Meta-Analysis

  • Haina Du ,

    Contributed equally to this work with: Haina Du, Nannan Guo, Bin Shi

    Affiliation Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Nannan Guo ,

    Contributed equally to this work with: Haina Du, Nannan Guo, Bin Shi

    Affiliation Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Bin Shi ,

    Contributed equally to this work with: Haina Du, Nannan Guo, Bin Shi

    Affiliation Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Qian Zhang,

    Affiliation Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Zhipeng Chen,

    Affiliation Department of Oncology, The first people's Hospital of Zhangjiagang City, Suzhou, China

  • Kai Lu,

    Affiliation Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Yongqian Shu,

    Affiliation Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Tao Chen ,

    ct55979@163.com (TC); zhulingjun@njmu.edu.cn (LZ)

    Affiliation Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

  • Lingjun Zhu

    ct55979@163.com (TC); zhulingjun@njmu.edu.cn (LZ)

    Affiliation Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

The Effect of XPD Polymorphisms on Digestive Tract Cancers Risk: A Meta-Analysis

  • Haina Du, 
  • Nannan Guo, 
  • Bin Shi, 
  • Qian Zhang, 
  • Zhipeng Chen, 
  • Kai Lu, 
  • Yongqian Shu, 
  • Tao Chen, 
  • Lingjun Zhu
PLOS
x

Abstract

Background

The Xeroderma pigmento-sum group D gene (XPD) plays a key role in nucleotide excision repair. Single nucleotide polymorphisms (SNP) located in its functional region may alter DNA repair capacity phenotype and cancer risk. Many studies have demonstrated that XPD polymorphisms are significantly associated with digestive tract cancers risk, but the results are inconsistent. We conducted a comprehensive meta-analysis to assess the association between XPD Lys751Gln polymorphism and digestive tract cancers risk. The digestive tract cancers that our study referred to, includes oral cancer, esophageal cancer, gastric cancer and colorectal cancer.

Methods

We searched PubMed and EmBase up to December 31, 2012 to identify eligible studies. A total of 37 case-control studies including 9027 cases and 16072 controls were involved in this meta-analysis. Statistical analyses were performed with Stata software (version 11.0, USA). Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association.

Results

The results showed that XPD Lys751Gln polymorphism was associated with the increased risk of digestive tract cancers (homozygote comparison (GlnGln vs. LysLys): OR = 1.12, 95% CI = 1.01–1.24, P = 0.029, P heterogeneity = 0.133). We found no statistical evidence for a significantly increased digestive tract cancers risk in the other genetic models. In the subgroup analysis, we also found the homozygote comparison increased the susceptibility of Asian population (OR = 1.28, 95% CI = 1.01–1.63, P = 0.045, P heterogeneity = 0.287). Stratified by cancer type and source of control, no significantly increased cancer risk was found in these subgroups. Additionally, risk estimates from hospital-based studies and esophageal studies were heterogeneous.

Conclusions

Our meta-analysis suggested that the XPD 751Gln/Gln genotype was a low-penetrate risk factor for developing digestive tract cancers, especially in Asian populations.

Introduction

Digestive tract cancers, especially gastric, esophageal and colorectal cancers, are a major global health problem. Globocan data in 2008 showed [1] that the standardized incidence of colorectal cancer, gastric cancer and esophageal cancer were located in 4th, 6th and 9th in all tumors, respectively. The standardized mortality rate of gastric cancer, coming after lung cancer and breast cancer, ranked the third place. Moreover, colorectal cancer and esophageal cancer also ranked top ten in cancer mortality rankings. The incidence of different cancer varies widely among different racial and ethnic groups which may be partly attributed to lifestyle and genetic background [2]. Exposure to environmental carcinogens can cause different types of DNA damage that subsequently lead to carcinogenesis of different tissues, if left unrepaired [3].

DNA repair mechanisms, such as the nucleotide excision repair (NER), base excision repair pathway (BER) and double-strand break pathway, are essential for maintaining genome integrity and preventing carcinogenesis. NER, the most versatile, well studied DNA repair mechanism in humans, is mainly responsible for repairing bulky DNA damage, such as DNA adducts caused by UV radiation, mutagenic chemicals, or chemotherapeutic drugs [4]. The major component of NER, xeroderma pigmentosum group D (XPD or ERCC2), mapped in chromosome 19q13.3, spans over 20 kb, contains 23exons and encodes the 761-amino acid protein. It has two functions: nucleotide excision repair and basal transcription as part of the transcription factor complex (TFIIH) [5]. Mutations on different sites in XPD gene can give rise to repair and transcription defects, and altered DNA repair capacity can render a higher risk of developing different types of cancer [5][11]. Several polymorphisms of XPD were identified, like Asp312Asn, Lys751Gln, Arg194Trp and Arg399Gln. The XPD polymorphic loci that has been of particular interest in molecular epidemiology studies is the Lys751Gln polymorphism (rs13181) in exon 23 [12]. The lysine to glutamine transition at position 751 in exon 23 may affect different protein interactions, diminish the activity of TFIIH complexes, and alter the genetic susceptibility to cancer [13].

Genetic variant in XPD Lys751Gln had been demonstrated to be associated with some cancers risk in different meta-analysis, such as esophageal cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, lung cancer and bladder cancer [14][23]. However, due to an insufficient number of publications, they did not calculate pooled odds ratios (ORs) of digestive tract cancers comprehensively. In consideration of the extensive role of XPD in digestive tract cancers, we performed a meta-analysis of all 37 eligible case–control studies: oral cancer, esophageal cancer, gastric cancer http://www.sciencedirect.com/science/article/pii/S0188440911000853 - bib10and colorectal cancer, to derive a more precise association of XPD Lys751Gln polymorphism and different types of digestive tract cancers risk.

Materials and Methods

Identification of eligible studies

Using PubMed, we identified all published case–control studies which investigated the association between the XPD Lys751Gln polymorphism and digestive tract cancers risk using a retrieving query formulation “(XPD or ERCC2) polymorphisms AND (colorectal cancer OR gastric cancer OR esophageal cancer OR oral cancer)”.The digestive tract cancers in this article refer to oral cancer, esophageal cancer, gastric cancer and colorectal cancer. We also searched references in published articles and reviews on this topic in PubMed. Eligible studies had to meet the following criteria: (a) only case-control designs were considered, (b) The study explored the correlation between different types of digestive tract cancers and XPD Lys751Gln polymorphism. Major exclusion criteria were (a) no control population, (b) no available genotype frequency. (c) Genotypic distribution of the controls was not in agreement with Hardy-Weinberg equilibrium (HWE). (d) Duplication of the previous publications, the largest or most recent publication was selected.

Data Extraction

Information was carefully extracted from all eligible publications independently by two authors according to the inclusion criteria listed above. If the two pieces of typed data were different, a third investigator would be asked to check and to make sure all data were right. The following information was extracted from each study: first author, year of publication, country of study population, ethnicity, source of controls, number of cases and controls with different genotypes and HWE (Table 1).

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Table 1. Characteristics of XPD polymorphisms Included in the Meta-analysis.

https://doi.org/10.1371/journal.pone.0096301.t001

Statistical Analysis

We assessed the departure from the Hardy–Weinberg equilibrium for the control group in each study using Pearson's goodness-of-fit χ2test with 1 degree of freedom. Heterogeneity among studies was checked by the random-effects model (the Der Simonian and Laird method) if there was significant heterogeneity [24]. A P value of more than the nominal level of 0.05 for the Q statistic indicated a lack of heterogeneity across studies, allowing for the use of the fixed -effects model (the Mantel–Haenszel method) [25]. If P value less than 0.05 was considered as having heterogeneity, the results can not be pooled together and discussed. The risks ORs of digestive tract cancers associated with the XPD Lys751Gln polymorphism were estimated for each study. The pooled ORs were evaluated on co-dominant model (Lys/Gln vs.Lys/Lys, Gln/Gln vs. Lys/Lys), dominant model (Gln/Gln + Lys/Gln vs. Lys/Lys), recessive model (Gln/Gln vs. Lys/Gln+Lys/Lys), respectively. Subgroup analyses were performed by cancer types, ethnicity and source of controls. The publication bias was diagnosed by the funnel plot, in which the standard error of log (OR) of each study was plotted against its log (OR). Funnel plot asymmetry was assessed by Egger's linear regression test. The significance of the intercept was determined by the t test suggested by Egger (P<0.05 was considered representative of statistically significant publication bias) [26]. All the statistical tests were performed with STATA version11.0 (Stata Corporation, College Station, TX, USA).

Results

Study characteristic

A total of 107 potential relevant studies were retrieved through PubMed (Figure 1). After carefully reviewing, 40 eligible case-control studies (3 studies not consistent with HWE were also shown) on the relationship between XPD Lys715Gln polymorphism and digestive cancers risk were involved in this meta-analysis, including 4 oral cancer studies [62][65], 13 esophageal cancer studies [27][39], 12 gastric cancer studies [36], [40][50] and 11 colorectal cancer studies [51][61]. As shown in Table 1, 17 studies were conducted in Asians, 20 studies in Europeans. In addition, there were 18 hospital-based studies, 19 population-based studies. Diverse genotyping methods were used, including PCR-RFLP, PCR-SSCP, Taqman, Real-time PCR and SEB PCR. All studies indicated that the genotypic distribution of the controls were consistent with HWE.

Meta-analysis

Table2 lists the main results of the meta-analysis for XPD Lys751Gln: having the Gln/Gln genotype is a risk factor for digestive tract cancers: GlnGln vs. LysLys: OR = 1.12, 95% CI = 1.01–1.24, P = 0.029, P heterogeneity = 0.133. I2 = 20.9% (Figure 2). We did not find any significant association between the other genetic models and digestive tract cancers. The results of stratified analysis by cancer type, source of controls and ethnicity were shown in table 2. The Gln/Gln vs. Lys/Lys genotype had an elevated risk in Asian population (OR = 1.28, 95% CI = 1.01–1.63, P = 0.045, P heterogeneity = 0.287, I2 = 14.2%; Figure 3). High heterogeneity was found in esophageal cancer and hospital-based studies, so the results can not be pooled together. In addition, the results did not suggest any association between XPD Lys751Gln polymorphism and digestive cancers susceptibility for all genetic models in European individuals or in population-based studies overall.

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Figure 2. Forest plot of digestive cancer risk associated with the XPD Lys751Gln polymorphisms.

Homozygote comparison.

https://doi.org/10.1371/journal.pone.0096301.g002

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Figure 3. Forest plot of digestive cancer risk associated with the XPD Lys751Gln polymorphisms in Asian subgroups (based on homozygote comparison).

A fixed-effects model was used. The squares and horizontal lines correspond to the study-specific OR and 95% CI. The area of the squares reflects the weight (inverse of the variance). The diamond represents the summary OR and 95% CI.

https://doi.org/10.1371/journal.pone.0096301.g003

Sensitivity analysis

In the sensitivity analysis, when each particular study had been removed meta-analyses were conducted repeatedly. The corresponding pooled ORs were not qualitatively altered with or without this study. As shown in Figure 4, the most influencing single study on the overall pooled OR estimates seemed to be the one conducted by Mariana et al, which had a relatively large sample size. However, after the removal of the study, the result of the meta-analysis did not been influenced significantly: Gln/Gln vs. Lys/Lys: OR = 1.17, 95% CI: 1.05–1.30, indicating high stability of our results.

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Figure 4. Influence analysis of the summary odds ratio coefficients on the association between XPD Lys751Gln homozygote comparison with digestive tract cancers risk.

Results were computed by omitting each study (left column) in turn. Bars, 95% CI.

https://doi.org/10.1371/journal.pone.0096301.g004

Heterogeneity analysis

There was moderate heterogeneity among these studies in GlnGln+GlnLys vs.LysLys comparisons and Gln/Gln vs. Lys/Lys comparisons, but not in the other genetic models. We explored the source of heterogeneity for dominant model by cancer type, ethnicity, source of control, and found that esophageal cancer and hospital-based studies contributed to substantial heterogeneity (Table3). One reason may be that hospital-based studies had relatively small samples and were more prone to random error and false positive or negative results. Furthermore, it is very likely that the heterogeneity in esophageal studies and hospital-based studies are related since hospital-based studies predominate among the esophageal studies.

Publication Bias

Begg's rank correlation method and Egger's weighted regression method were used to assess publication bias. There was no evidence of publication bias in XPD Lys751Gln (Begg's test P = 0.284, Egger's test P = 0.324, t = 1.00, 95% CI = 0.41–1.21). We present funnel plot for ORs of Gln/Gln versus Lys/Lys (Figure 5).

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Figure 5. Begg's funnel plot for publication bias test (Homozygote comparison).

Each point represents a separate study for the indicated association.

https://doi.org/10.1371/journal.pone.0096301.g005

Discussion

XPD plays a crucial role in NER, which is significant in the elimination of certain DNA cross-links, ultraviolet (UV) photo-lesions, and bulky chemical adducts. The XPD protein possesses both single-strand DNA-dependant ATP ase and 5′-3′ DNA helicase activities, which is essential for NER pathway and transcription [66]. Genetic variation in XPD may contribute to impaired DNA repair capacity and increased cancer risk. The Lys to Gln change at position 751 of XPD results in complete changes about the charge configuration of the amino acid, which affects the interactions of XPD protein and its helicase activator [67]. To date, a number of epidemiological studies have been conducted to evaluate the role of Lys751Gln polymorphism on several cancer risks, but the results remain controversial. As far as we know, several previous meta-analyses on XPD Lys751Gln polymorphism and cancers risk have been performed, such as gastric cancer, colorectal cancer, esophageal cancer, breast cancer and bladder cancer [14][23]. But to date, there is no meta-analysis on the association between digestive tract cancers risk and XPD Lys751Gln polymorphism. In order to derive a more precise estimation of relationship, we performed this meta-analysis of 37 studies, including 9027 cases and 16072 controls.

Through analyzing genotypes from the 37 eligible studies, we found the Gln/Gln genotype carries might be at potential risk to digestive tract cancers. The Lys to Gln variation on position 751 of XPD resulted in complete changes about the electronic configuration of the amino acid, which affected the interactions of XPD protein and its helicase activator [68]. Digestive tract cancers represent a homogenous group of malignancies in some ways. Different primary sites of digestive tract cancers have some shared risk factors. For example, except for smoking and alcohol consumption, eating rough, spicy, hot and non-digestible food is likely to damage the digestive tract tissue. In addition, H.Pylori infection is a major cause of gastric cancer, while nitrites derived from red meat and processed meat is a key risk factor for esophageal cancer and colorectal cancer. Such risk factors and their tissue specificity raise the possibility that the XPD polymorphism may be associated with digestive tract cancers risk. The functional XPD Lys751Gln polymorphism resulting in decreased activity of XPD protein may increase risk of digestive tract cancers on the basis of damage tissue.

In stratified analysis by cancer type, we found that all genetic models did not appear to have an effect on the risks of esophageal, gastric, colorectal and oral cancers. This was different from Ling Yuan's and Wu XB's studies [69], [70]. However Bo Chen et al. [71] detected that Gln/Gln genotype carriers might have an increased risk of gastric cancer in the Helico-bacter pylori (H.pylori)-positive population, but not in the Helico-bacter pylori (H. pylori)-negative population. One possible explanation is that the modulation of digestive tract cancers risk may depend not only on a single gene/single nucleotide polymorphism, but also on a joint effect of multiple polymorphisms within different genes or pathways, or on close interaction between polymorphisms and environmental factor. The other is that Helicobacter pylori infection is one of the clear etiologies of gastric cancer and maybe there is some relationship between helicobacter pylori and the polymorphic loci. In the subgroup of ethnicity, we found significant association between XPD Gln/Gln polymorphism and increased risks of digestive tract cancers in Asians but not in European. We think ethnic differences and diverse live environment may partly explain the phenomenon. Furthermore, we believed differences in diet, such as food structure and cooking way, were the main cause of this result. In addition, it was also likely that the observed ethnic differences may be due to chance because studies with small sample size may have insufficient statistical power to detect a slight effect or may have generated a fluctuated risk estimate [72].

In summary, this meta-analysis indicated that XPD Lys751Gln polymorphism, individuals carrying the variant homozygote Gln/Gln may increase the susceptibility of digestive tract cancers. And, significant associations were detected among Asians population. It should be noted explicitly: first, the effective sample size is much smaller for the Gln/Gln vs. Lys/Lys analyses than the other genetic models and therefore it is more prone to random error and false positive results; second, the results for GlnGln vs. GlyLys+LysLys, while not statistically significant (OR 1.09, 95% CI = 0.99–1.20, P = 0.072, P heterogeneity = 0.385), strengthen our conclusion about which genetic model is most appropriate. Large-scale case-control and population-based association studies are warranted to validate the risk identified in the current meta-analysis and investigate the potential gene-gene and gene-environment interactions on digestive tract cancers risk.

Author Contributions

Conceived and designed the experiments: HND NNG YQS TC LJZ. Performed the experiments: HND BS QZ ZPC KL TC LJZ. Analyzed the data: HND ZPC LJZ QZ. Contributed reagents/materials/analysis tools: HND ZPC LJZ QZ. Wrote the paper: HND ZPC NNG. Designed the software used in analysis: HND NNG ZPC QZ.

References

  1. 1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127: 2893–2917.
  2. 2. Iscovich J, Howe GR (1998) Cancer incidence patterns (1972–91) among migrants from the Soviet Union to Israel. Cancer Causes Control 9: 29–36.
  3. 3. Zhu ML, Wang M, Cao ZG, He J, Shi TY, et al. (2012) Association between the ERCC5 Asp1104His polymorphism and cancer risk: a meta-analysis. PLoS One 7: e36293.
  4. 4. Shi TY, He J, Qiu LX, Zhu ML, Wang MY, et al. (2012) Association between XPF polymorphisms and cancer risk: a meta-analysis. PLoS One 7: e38606.
  5. 5. Spitz MR, Wu X, Wang Y, Wang LE, Shete S, et al. (2001) Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 61: 1354–1357.
  6. 6. Shen H, Spitz MR, Qiao Y, Guo Z, Wang LE, et al. (2003) Smoking, DNA repair capacity and risk of nonsmall cell lung cancer. Int J Cancer 107: 84–88.
  7. 7. Shi Q, Wang LE, Bondy ML, Brewster A, Singletary SE, et al. (2004) Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients. Carcinogenesis 25: 1695–1700.
  8. 8. Ramos JM, Ruiz A, Colen R, Lopez ID, Grossman L, et al. (2004) DNA repair and breast carcinoma susceptibility in women. Cancer 100: 1352–1357.
  9. 9. Wei Q, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, et al. (2003) Repair of UV light-induced DNA damage and risk of cutaneous malignant melanoma. J Natl Cancer Inst 95: 308–315.
  10. 10. Hu JJ, Hall MC, Grossman L, Hedayati M, McCullough DL, et al. (2004) Deficient nucleotide excision repair capacity enhances human prostate cancer risk. Cancer Res 64: 1197–1201.
  11. 11. Hemminki K, Xu G, Angelini S, Snellman E, Jansen CT, et al. (2001) XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 22: 1185–1188.
  12. 12. Shen MR, Jones IM, Mohrenweiser H (1998) Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58: 604–608.
  13. 13. Shen MR, Jones IM, Mohrenweiser H (1998) Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58: 604–608.
  14. 14. Xue H, Lu Y, Lin B, Chen J, Tang F, et al. (2012) The effect of XPD/ERCC2 polymorphisms on gastric cancer risk among different ethnicities: a systematic review and meta-analysis. PLoS One 7: e43431.
  15. 15. Zhu S, Zhang H, Tang Y, Wang J (2012) Polymorphisms in XPD and hOGG1 and prostate cancer risk: a meta-analysis. Urol Int 89: 233–240.
  16. 16. Yuan H, Niu YM, Wang RX, Li HZ, Chen N (2011) Association between XPD Lys751Gln polymorphism and risk of head and neck cancer: a meta-analysis. Genet Mol Res 10: 3356–3364.
  17. 17. Ding DP, Ma WL, He XF, Zhang Y (2012) XPD Lys751Gln polymorphism and esophageal cancer susceptibility: a meta-analysis of case-control studies. Mol Biol Rep 39: 2533–2540.
  18. 18. Yuan L, Cui D, Zhao EJ, Jia CZ, Wang LD, et al. (2011) XPD Lys751Gln polymorphism and esophageal cancer risk: a meta-analysis involving 2288 cases and 4096 controls. World J Gastroenterol 17: 2343–2348.
  19. 19. Zhang Y, Ding D, Wang X, Zhu Z, Huang M, et al. (2011) Lack of association between XPD Lys751Gln and Asp312Asn polymorphisms and colorectal cancer risk: a meta-analysis of case-control studies. Int J Colorectal Dis 26: 1257–1264.
  20. 20. Zhan P, Wang Q, Wei SZ, Wang J, Qian Q, et al. (2010) ERCC2/XPD Lys751Gln and Asp312Asn gene polymorphism and lung cancer risk: a meta-analysis involving 22 case-control studies. J Thorac Oncol 5: 1337–1345.
  21. 21. Pabalan N, Francisco-Pabalan O, Sung L, Jarjanazi H, Ozcelik H (2010) Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer. Breast Cancer Res Treat 124: 531–541.
  22. 22. Qiu LX, Yao L, Zhang J, Zhu XD, Zhao XM, et al. (2010) XPD Lys751Gln polymorphism and breast cancer susceptibility: a meta-analysis involving 28,709 subjects. Breast Cancer Res Treat 124: 229–235.
  23. 23. Wang M, Gu D, Zhang Z, Zhou J (2009) XPD polymorphisms, cigarette smoking, and bladder cancer risk: a meta-analysis. J Toxicol Environ Health A 72: 698–705.
  24. 24. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7: 177–188.
  25. 25. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22: 719–748.
  26. 26. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315: 629–634.
  27. 27. Huang CG, Liu T, Lv GD, Liu Q, Feng JG, et al. (2012) Analysis of XPD genetic polymorphisms of esophageal squamous cell carcinoma in a population of Yili Prefecture, in Xinjiang, China. Mol Biol Rep 39: 709–714.
  28. 28. Liu G, Zhou W, Yeap BY, Su L, Wain JC, et al. (2007) XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis 28: 1254–1258.
  29. 29. Xing DY, Qi J, Tan W, Miao XP, Liang G, et al. (2003) Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20: 35–38.
  30. 30. Xing D, Qi J, Miao X, Lu W, Tan W, et al. (2002) Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Int J Cancer 100: 600–605.
  31. 31. Xing D, Tan W, Lin D (2003) Genetic polymorphisms and susceptibility to esophageal cancer among Chinese population (review). Oncol Rep 10: 1615–1623.
  32. 32. Yu HP, Wang XL, Sun X, Su YH, Wang YJ, et al. (2004) Polymorphisms in the DNA repair gene XPD and susceptibility to esophageal squamous cell carcinoma. Cancer Genet Cytogenet 154: 10–15.
  33. 33. Casson AG, Zheng Z, Evans SC, Veugelers PJ, Porter GA, et al. (2005) Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. Carcinogenesis 26: 1536–1541.
  34. 34. Ye W, Kumar R, Bacova G, Lagergren J, Hemminki K, et al. (2006) The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden. Carcinogenesis 27: 1835–1841.
  35. 35. Tse D, Zhai R, Zhou W, Heist RS, Asomaning K, et al. (2008) Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer Causes Control 19: 1077–1083.
  36. 36. Doecke J, Zhao ZZ, Pandeya N, Sadeghi S, Stark M, et al. (2008) Polymorphisms in MGMT and DNA repair genes and the risk of esophageal adenocarcinoma. Int J Cancer 123: 174–180.
  37. 37. Ferguson HR, Wild CP, Anderson LA, Murphy SJ, Johnston BT, et al. (2008) No association between hOGG1, XRCC1, and XPD polymorphisms and risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma: results from the factors influencing the Barrett's adenocarcinoma relationship case-control study. Cancer Epidemiol Biomarkers Prev 17: 736–739.
  38. 38. Pan J, Lin J, Izzo JG, Liu Y, Xing J, et al. (2009) Genetic susceptibility to esophageal cancer: the role of the nucleotide excision repair pathway. Carcinogenesis 30: 785–792.
  39. 39. Xing DY, Qi J, Tan W, Miao XP, Liang G, et al. (2003) Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20: 35–38.
  40. 40. Lou Y, Song Q, He XM (2006) Association of single nucleotide polymorphism in DNA repair gene XPD with gastric cancer in Han population from northeast region of China. World Chinese Journal of Digestology 14: 3143–3146.
  41. 41. Canbay E, Agachan B, Gulluoglu M, Isbir T, Balik E, et al. (2010) Possible associations of APE1 polymorphism with susceptibility and HOGG1 polymorphism with prognosis in gastric cancer. Anticancer Res 30: 1359–1364.
  42. 42. Palli D, Polidoro S, D'Errico M, Saieva C, Guarrera S, et al. (2010) Polymorphic DNA repair and metabolic genes: a multigenic study on gastric cancer. Mutagenesis 25: 569–575.
  43. 43. Zhang CZ, Chen ZP, Xu CQ, Ning T, Li DP, et al. (2009) Correlation of XPD gene with susceptibility to gastric cancer. Ai Zheng 28: 1163–1167.
  44. 44. Ruzzo A, Canestrari E, Maltese P, Pizzagalli F, Graziano F, et al. (2007) Polymorphisms in genes involved in DNA repair and metabolism of xenobiotics in individual susceptibility to sporadic diffuse gastric cancer. Clin Chem Lab Med 45: 822–828.
  45. 45. Capella G, Pera G, Sala N, Agudo A, Rico F, et al. (2008) DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study. Int J Epidemiol 37: 1316–1325.
  46. 46. Ye W, Kumar R, Bacova G, Lagergren J, Hemminki K, et al. (2006) The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden. Carcinogenesis 27: 1835–1841.
  47. 47. Zhou RM, Li Y, Wang N, Zhang XJ, Dong XJ, et al. (2006) [Correlation of XPC Ala499Val and Lys939Gln polymorphisms to risks of esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma]. Ai Zheng 25: 1113–1119.
  48. 48. Engin AB, Karahalil B, Engin A, Karakaya AE (2011) DNA repair enzyme polymorphisms and oxidative stress in a Turkish population with gastric carcinoma. Mol Biol Rep 38: 5379–5386.
  49. 49. Long XD, Ma Y, Huang YZ, Yi Y, Liang QX, et al. (2010) Genetic polymorphisms in DNA repair genes XPC, XPD, and XRCC4, and susceptibility to Helicobacter pylori infection-related gastric antrum adenocarcinoma in Guangxi population, China. Mol Carcinog 49: 611–618.
  50. 50. Huang WY, Chow WH, Rothman N, Lissowska J, Llaca V, et al. (2005) Selected DNA repair polymorphisms and gastric cancer in Poland. Carcinogenesis 26: 1354–1359.
  51. 51. Canbay E, Cakmakoglu B, Zeybek U, Sozen S, Cacina C, et al. (2011) Association of APE1 and hOGG1 polymorphisms with colorectal cancer risk in a Turkish population. Curr Med Res Opin 27: 1295–1302.
  52. 52. Jelonek K, Gdowicz-Klosok A, Pietrowska M, Borkowska M, Korfanty J, et al. (2010) Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. J Appl Genet 51: 343–352.
  53. 53. Wang J, Zhao Y, Jiang J, Gajalakshmi V, Kuriki K, et al. (2010) Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case-control study in an Indian population. J Cancer Res Clin Oncol 136: 1517–1525.
  54. 54. Sliwinski T, Krupa R, Wisniewska-Jarosinska M, Pawlowska E, Lech J, et al. (2009) Common polymorphisms in the XPD and hOGG1 genes are not associated with the risk of colorectal cancer in a Polish population. Tohoku J Exp Med 218: 185–191.
  55. 55. Skjelbred CF, Saebo M, Wallin H, Nexo BA, Hagen PC, et al. (2006) Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study. BMC Cancer 6: 67.
  56. 56. Hansen RD, Sorensen M, Tjonneland A, Overvad K, Wallin H, et al. (2007) XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer. Mutat Res 619: 68–80.
  57. 57. Stern MC, Conti DV, Siegmund KD, Corral R, Yuan JM, et al. (2007) DNA repair single-nucleotide polymorphisms in colorectal cancer and their role as modifiers of the effect of cigarette smoking and alcohol in the Singapore Chinese Health Study. Cancer Epidemiol Biomarkers Prev 16: 2363–2372.
  58. 58. Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, et al. (2006) Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res 12: 2101–2108.
  59. 59. Yeh CC, Sung FC, Tang R, Chang-Chieh CR, Hsieh LL (2007) Association between polymorphisms of biotransformation and DNA-repair genes and risk of colorectal cancer in Taiwan. J Biomed Sci 14: 183–193.
  60. 60. Stern MC, Siegmund KD, Conti DV, Corral R, Haile RW (2006) XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 15: 2384–2390.
  61. 61. Skjelbred CF, Saebo M, Wallin H, Nexo BA, Hagen PC, et al. (2006) Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study. BMC Cancer 6: 67.
  62. 62. Bau DT, Tsai MH, Huang CY, Lee CC, Tseng HC, et al. (2007) Relationship between polymorphisms of nucleotide excision repair genes and oral cancer risk in Taiwan: evidence for modification of smoking habit. Chin J Physiol 50: 294–300.
  63. 63. Majumder M, Sikdar N, Ghosh S, Roy B (2007) Polymorphisms at XPD and XRCC1 DNA repair loci and increased risk of oral leukoplakia and cancer among NAT2 slow acetylators. Int J Cancer 120: 2148–2156.
  64. 64. Ramachandran S, Ramadas K, Hariharan R, Rejnish Kumar R, Radhakrishna Pillai M (2006) Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer. Oral Oncol 42: 350–362.
  65. 65. Kietthubthew S, Sriplung H, Au WW, Ishida T (2006) Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand. Int J Hyg Environ Health 209: 21–29.
  66. 66. Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, et al. (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21: 551–555.
  67. 67. Pavanello S, Pulliero A, Siwinska E, Mielzynska D, Clonfero E (2005) Reduced nucleotide excision repair and GSTM1-null genotypes influence anti-B[a]PDE-DNA adduct levels in mononuclear white blood cells of highly PAH-exposed coke oven workers. Carcinogenesis 26: 169–175.
  68. 68. Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, et al. (1998) Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet 20: 184–188.
  69. 69. Yuan L, Cui D, Zhao EJ, Jia CZ, Wang LD, et al. (2011) XPD Lys751Gln polymorphism and esophageal cancer risk: a meta-analysis involving 2288 cases and 4096 controls. World J Gastroenterol 17: 2343–2348.
  70. 70. Wu XB, Dai LP, Wang YP, Wang KJ, Zhang JY (2009) [DNA repair gene xeroderma pigmentosum group D 751 polymorphism and the risk on esophageal cancer: a meta-analysis]. Zhonghua Liu Xing Bing Xue Za Zhi 30: 281–285.
  71. 71. Chen B, Zhou Y, Yang P, Wu XT (2011) ERCC2 Lys751Gln and Asp312Asn polymorphisms and gastric cancer risk: a meta-analysis. J Cancer Res Clin Oncol 137: 939–946.
  72. 72. Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N (2004) Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst 96: 434–442.