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Human Genetics

, Volume 131, Issue 7, pp 1235–1244 | Cite as

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

  • Jing He
  • Li-Xin Qiu
  • Meng-Yun Wang
  • Rui-Xi Hua
  • Ruo-Xin Zhang
  • Hong-Ping Yu
  • Ya-Nong Wang
  • Meng-Hong Sun
  • Xiao-Yan Zhou
  • Ya-Jun Yang
  • Jiu-Cun Wang
  • Li Jin
  • Qing-Yi Wei
  • Jin Li
Original Investigation

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.

Keywords

Gastric Cancer Nucleotide Excision Repair Lymphoblastoid Cell Line Xeroderma Pigmentosum Gastric Cancer Risk 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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

Notes

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.

Supplementary material

439_2012_1152_MOESM1_ESM.doc (104 kb)
Supplementary material 1 (DOC 103 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Jing He
    • 1
    • 2
    • 3
  • Li-Xin Qiu
    • 1
    • 2
    • 3
  • Meng-Yun Wang
    • 2
    • 3
  • Rui-Xi Hua
    • 1
    • 2
  • Ruo-Xin Zhang
    • 2
    • 3
  • Hong-Ping Yu
    • 4
  • Ya-Nong Wang
    • 5
  • Meng-Hong Sun
    • 6
  • Xiao-Yan Zhou
    • 6
  • Ya-Jun Yang
    • 7
    • 8
  • Jiu-Cun Wang
    • 7
    • 8
  • Li Jin
    • 7
    • 8
  • Qing-Yi Wei
    • 3
    • 4
  • Jin Li
    • 1
    • 2
  1. 1.Department of Medical OncologyFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Cancer Research LaboratoryFudan University Shanghai Cancer CenterShanghaiChina
  4. 4.Department of EpidemiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Department of Abdominal SurgeryFudan University Shanghai Cancer CenterShanghaiChina
  6. 6.Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
  7. 7.State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences and Institutes of Biomedical SciencesFudan UniversityShanghaiChina
  8. 8.Fudan-Taizhou Institute of Health SciencesTaizhouChina

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