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Tumor Biology

, Volume 36, Issue 12, pp 9525–9535 | Cite as

Effect of ERCC8 tagSNPs and their association with H. pylori infection, smoking, and alcohol consumption on gastric cancer and atrophic gastritis risk

  • Jing-jing Jing
  • Li-ping Sun
  • Qian Xu
  • Yuan Yuan
Research Article

Abstract

Excision repair cross-complementing group 8 (ERCC8) plays a critical role in DNA repair. Genetic polymorphisms in ERCC8 may contribute to the risk of cancer development. We selected tag single nucleotide polymorphisms (tagSNPs) in Chinese patients from the HapMap database to investigate associations with gastric cancer and its precursors. Genomic DNA was extracted from 394 controls, 394 atrophic gastritis, and 394 gastric cancer cases in northern Chinese patients, and genotypes were identified using the Sequenom MassARRAY system. We found that the ERCC8 rs158572 GG+GA genotype showed a 1.651-fold (95 % confidence interval (CI) = 1.109–2.457, P = 0.013) increased risk of gastric cancer compared with the AA genotype, especially in diffuse type. Stratified analysis comparing the common genotype revealed significantly increased gastric cancer risk in males and individuals older than 50 years with rs158572 GA/GG/GG+GA genotypes, while individuals older than 50 years with rs158916 CT/CC+CT genotypes were less susceptible to atrophic gastritis. Haplotype analysis showed that the G-T haplotype was associated with increased risk of gastric cancer. Statistically significant interactions between the two ERCC8 tagSNPs and Helicobacter pylori infection were observed for gastric cancer and atrophic gastritis risk (P < 0.05). Smokers and drinkers with ERCC8 rs158572 GG+GA genotype were more susceptible to gastric cancer compared with non-smokers and non-drinkers homozygous for AA. Our findings suggested that ERCC8 rs158572 and rs158916, alone or together with environmental factors, might be associated with gastric cancer and atrophic gastritis susceptibility. Further validation of our results in larger populations along with additional studies evaluating the underlying molecular function is required.

Keywords

ERCC8 TagSNP Gastric cancer Atrophic gastritis Susceptibility 

Notes

Acknowledgments

This work is supported by grants from the National Key Basic Research Program of China (973 Program Ref No.2010CB529304) and the National Natural Science Foundation of China (Ref No.31200968).

Authors’ contributions

YY conceived and designed the experiments and revised the manuscript. JJ and QX performed the experiments. JJ and LS analyzed the data. LS and QX collected the serum/biopsy samples. YY contributed the reagents/materials/analysis tools. JJ and YY wrote the paper.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jing-jing Jing
    • 1
    • 2
  • Li-ping Sun
    • 1
    • 2
  • Qian Xu
    • 1
    • 2
  • Yuan Yuan
    • 1
    • 2
  1. 1.Tumor Etiology and Screening Department of Cancer Institute and General SurgeryThe First Affiliated Hospital of China Medical UniversityShenyang CityChina
  2. 2.Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education DepartmentChina Medical UniversityShenyangChina

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