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Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a meta-analysis

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Tumor Biology

Abstract

Numerous epidemiological studies have been conducted to investigate the association between Xeroderma pigmentosum complementation group D (XPD) Asp312Asn (rs1799793 G > A) and Lys751Gln (rs13181 A > C) polymorphisms and bladder cancer risk; however, the conclusions remain controversial. With this in mind, we performed this meta-analysis with 11 studies including 3,797 cases and 5,094 controls for Asp312Asn and 21 studies including 6,360 cases and 7,894 controls for Lys751Gln polymorphism. We searched available literatures from PubMed, Embase, and CBM databases. Crude odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to assess the strength of the associations. Moreover, to validate biological plausibility of our findings, the effects of these two polymorphisms on XPD gene expression within three ethnicities was determine by gene expression analysis based on imputed genotypes from HapMap. Overall, the variant allele of Asp312Asn polymorphism was associated with an increased risk of bladder cancer (Asn/Asn vs. Asp/Asp: OR = 1.51, 95 % CI = 1.19–1.91; Asp/Asn vs. Asp/Asp: OR = 1.23, 95 % CI = 1.12–1.35; recessive model: OR = 1.33, 95 % CI = 1.10–1.61; dominant model: OR = 1.32, 95 % CI = 1.14–1.52; and allele comparing: OR = 1.26, 95 % CI = 1.11–1.42). We found the Lys751Gln was associated with increased bladder cancer risk only under the recessive model (OR = 1.14, 95 % CI = 1.01–1.29). Stratification analyses demonstrated an increased risk for Asians and hospital-based studies under all genetic models while only under the dominant model for Caucasians as to the Asp312Asn polymorphism and for Caucasians under the recessive model as to the Lys751Gln polymorphism. We also found the Asp312Asn polymorphism can significantly influence mRNA expression levels among Asians and Caucasians, and the Lys751Gln polymorphism has a similar effect for Caucasians. Despite some limitations, this meta-analysis suggests that polymorphisms in XPD gene may contribute to bladder cancer susceptibility. These findings need further validation by large well-designed prospective studies.

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Abbreviations

NER:

nucleotide excision repair

SNP:

single nucleotide polymorphism

DRC:

DNA repair capacity

XPD:

Xeroderma pigmentosum complementation group D

CBM:

Chinese Biomedical

OR:

Odds ratio

CI:

Confidence interval

HWE:

Hardy–Weinberg equilibrium

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Acknowledgments

This work was supported by a grant funded by Heilongjiang Education Department of China (1252HQ016).

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Authors and Affiliations

  1. Department of Tumor Rehabilitation, First Hospital, Wenzhou Medical University, No.2 Fuxue Lane, Wenzhou, Zhejiang, 325000, China

    Su-** Road, Harbin, Heilongjiang, 150040, China

    **-Hong Zhu

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  1. Su-**a Li
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  2. Qiang-Sheng Dai
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  3. Su-**u Chen
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  4. Shao-Dan Zhang
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  5. **ao-Yu Liao
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  7. Hong-Bo Chi
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  8. Feng-Jie Li
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  9. **-Hong Zhu
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  10. Yi-Yan Jiang
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Corresponding authors

Correspondence to **-Hong Zhu or Yi-Yan Jiang.

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Li and Dai contributed equally to this study and should be considered as co-first authors.

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Li, SX., Dai, QS., Chen, SX. et al. Xeroderma pigmentosum complementation group D (XPD) gene polymorphisms contribute to bladder cancer risk: a meta-analysis. Tumor Biol. 35, 3905–3915 (2014). https://doi.org/10.1007/s13277-013-1519-z

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  • DOI: https://doi.org/10.1007/s13277-013-1519-z

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