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Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations

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Abstract

DNA repair genes play an important role in maintaining stability and integrity of genomic DNA. Polymorphisms in nucleotide excision repair genes may cause variations in DNA repair capacity phenotype and thus contribute to cancer risk. In this case–control study of 1,125 gastric cancer cases and 1,196 cancer-free controls, we investigated the association between three functional single nucleotide polymorphisms (SNPs, rs2296147T > C, rs2094258C > T and rs873601G > A) in the xeroderma pigmentosum group G (XPG) gene and gastric cancer risk. We used the Taqman assays to genotype these three SNPs and logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found that only the rs873601A variant genotypes were associated with a significant higher risk for gastric adenocarcinoma (adjusted OR = 1.30, 95% CI = 1.03–1.64 for AA vs. GG and adjusted OR = 1.23, 95% CI = 1.01–1.49 for AA vs. GG/AG). Stratification analysis indicated that this risk was more pronounced in subgroups of older age (>59 years), males, ever-smokers, and patients with NGCA. All these were not found for the other two SNPs (rs2296147T > C and rs2094258C > T). We then performed expression analysis using gastric cancer adjacent normal tissues from 141 patients and found that the A variant allele was associated with non-significantly reduced expression of XPG mRNA (P trend = 0.107). Further analysis using mRNA expression data from the HapMap suggested that the A allele was associated with significantly reduced expression of XPG mRNA in normal cell lines for 45 Chinese (P trend = 0.003) as well as for 261 subjects with different ethnicities (P trend = 0.001). These support the hypothesis that functional XPG variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.

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Abbreviations

NER:

Nucleotide excision repair

SNP:

Single nucleotide polymorphism

XPG :

Xeroderma pigmentosum group G

CI:

Confidence interval

OR:

Odds ratio

GCA:

Gastric cardia adenocarcinoma

NGCA:

Non-gastric cardia adenocarcinoma

UTR:

Untranslated region

CHB:

Han Chinese in Beijing, China

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Acknowledgments

This study was supported by the grant from “China’s Thousand Talents Program” Recruitment at Fudan University, the grant from the Ministry of Health (201002007) and the National Natural Science Foundation of China (81101808). We thank Zhuan-Xu Zhang and Huan Chen for his assistance in DNA extraction and Yu-Hu Xin for his technical support.

Conflict of interest

None declared.

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Authors and Affiliations

  1. Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China

    Jing He, Li-Xin Qiu, Rui-Xi Hua & Jin Li

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Jing He, Li-Xin Qiu, Meng-Yun Wang, Rui-Xi Hua, Ruo-Xin Zhang & Jin Li

  3. Cancer Research Laboratory, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai, 200032, China

    Jing He, Li-Xin Qiu, Meng-Yun Wang, Ruo-Xin Zhang & Qing-Yi Wei

  4. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Hong-Ping Yu & Qing-Yi Wei

  5. Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

    Ya-Nong Wang

  6. Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

    Meng-Hong Sun & Xiao-Yan Zhou

  7. State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical Sciences, Fudan University, Shanghai, China

    Ya-Jun Yang, Jiu-Cun Wang & Li Jin

  8. Fudan-Taizhou Institute of Health Sciences, 1 Yaocheng Road, Taizhou, Jiangsu, 225300, China

    Ya-Jun Yang, Jiu-Cun Wang & Li Jin

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  1. Jing He
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  2. Li-Xin Qiu
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  12. Li Jin
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  13. Qing-Yi Wei
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  14. Jin Li
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Corresponding authors

Correspondence to Qing-Yi Wei or Jin Li.

Additional information

J. He and L.-X. Qiu contributed equally to this work and should be considered as co-first authors.

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He, J., Qiu, LX., Wang, MY. et al. Polymorphisms in the XPG gene and risk of gastric cancer in Chinese populations. Hum Genet 131, 1235–1244 (2012). https://doi.org/10.1007/s00439-012-1152-8

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  • DOI: https://doi.org/10.1007/s00439-012-1152-8

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