Skip to main content
SpringerLink
Log in

PARP1 Polymorphisms Increase the Risk of Gastric Cancer in a Chinese Population

  • Original Research Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Background and Objective: Poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1), a protein involved in the DNA repair mechanism, plays an important role in carcinogenesis. In this study, we investigated whether single nucleotide polymorphisms of PARP1 contribute to gastric cancer (GC) and its precursor lesions (gastric precancerous lesions; GPL) in a case-control study conducted in the Hexi area of China, a high-risk area for GC.

Methods: PARP1 162C>G (Phe54Leu) and 2819A>G (Lys940Arg) polymorphisms were genotyped by realtime PCR using a TaqMan assay in 140 GC cases, 110 GPL cases, and 120 controls. Data were statistically analyzed using the chi-squared test and a logistic regression model.

Results: The presence of the PARP1 2819G allele was associated with an increased risk of GC (odds ratio [OR] 2.354; 95% CI 1.140, 4.861; p = 0.018), especially for cardia GC and diffuse-type GC (ORs 2.988 and 3.784, respectively). We also observed an interaction between Helicobacter pylori infection, GC family history, and the presence of the PARP1 2819G allele. In contrast, the PARP1 162C>G polymorphism wasnot significantly associated with GPL or GC.

Conclusion: The study suggests that the PARP1 2819G allele is associated with an increased risk of GC. In addition, H. pylori-positive status and family history jointly contribute to a higher risk of GC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table II
Table III
Table IV
Table V

Similar content being viewed by others

References

  1. Garcia M, Jemal A, Ward EM, et al. Global cancer facts and figures 2007. Atlanta (GA): American Cancer Society, 2007 [online]. Available from URL: http://www.cancer.org/acs/groups/content/@nho/documents/document/globalfactsandfigures2007rev2p.pdf [Accessed 2011 Nov 30]

    Google Scholar 

  2. De Vries AC, Casparie MK, Van Griecken NC, et al. Epidemiological trends of pre-malignant gastric lesions: a long-term nationwide study in the Netherlands. Gastroenterology 2007; 56: 1665–70

    Google Scholar 

  3. Duarte MC, Colombo J, Rossit ARB, et al. Polymorphisms of DNA repair genes XRCC1 and XRCC3, interaction with environmental exposure and risk of chronic gastritis and gastric cancer. World J Gastroenterol 2005; 11: 6593–600

    PubMed  CAS  Google Scholar 

  4. Ward MH, Heineman EF, Markin RS, et al. Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite. Int J Occup Env Heal 2008; 14: 193–7

    CAS  Google Scholar 

  5. Schreiber V, Datzer F, Ame JC, et al. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 2006; 7: 517–28

    Article  PubMed  CAS  Google Scholar 

  6. Cohen-Armon M, Visochek L, Rozensal D, et al. DNA-independent PARP-1 activation by phosphorylated ERK2 increases EIk1 activity: a link to histone acetylation. Mol Cell 2007; 25: 297–308

    Article  PubMed  CAS  Google Scholar 

  7. Wang XG, Wang ZQ, Tong WM, et al. PARP1 Val762Ala polymorphism reduces enzymatic activity. Biochem Biophys Res Commun 2007; 354: 122–6

    Article  PubMed  CAS  Google Scholar 

  8. Cao WH, Wang X, Frappart L, et al. Analysis of genetic variants of the poly(ADP-ribose) polymerase-1 gene in breast cancer in French patients. Mutat Res 2007; 632: 20–8

    Article  PubMed  CAS  Google Scholar 

  9. Cottet F, Blanche H, Verasdonck P, et al. New polymorphisms in the human poly(ADP-ribose) polymerase-1 coding sequence: lack of association with longevity or with increased cellular poly(ADP-ribosyl)ation capacity. J Mol Med 2000; 78: 431–40

    Article  PubMed  CAS  Google Scholar 

  10. Mohrenweiser HW, Xi T, Vazquez-Matias J, et al. Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans. Cancer Epidemiol Biomark Prev 2002; 11: 1054–64

    CAS  Google Scholar 

  11. Motoko S, Mitsuko M, Hisako F, et al. Genetic alteration of poly(ADP-ribose) polymerase-1 in human germ cell tumors. Jpn J Clin Oncol 2005; 35: 97–102

    Article  Google Scholar 

  12. Zhang QB, Li YM, Li X, et al. PARP-1 Val762Ala polymorphism, CagA+ H. pylori infection and risk for gastric cancer in Han Chinese population. Mol Biol Rep 2009; 36: 1461–7

    Article  PubMed  CAS  Google Scholar 

  13. Nguewa PA, Fuertes MA, Valladares B, et al. Poly(ADP-ribose) polymerases: homology, structural domains and functions: novel therapeutical applications. Prog Biophys Mol Biol 2005; 88: 143–72

    Article  PubMed  CAS  Google Scholar 

  14. World Health Organization. Guidelines for drinking-water quality, third edition, incorporating first and second addenda. Geneva: World Health Organization, 2008 [online]. Available from URL: http://www.who.int/water_sanitation_health/dwq/fulltext.pdf [Accessed 2011 Nov 30]

    Google Scholar 

  15. Peralta-Leal A, Rodriguez-Vargas JM, Aguilar-Quesada R, et al. PARP inhibitors: new partners in the therapy of cancer and inflammatory diseases. Free Radical Bio Med 2009; 47: 13–26

    Article  CAS  Google Scholar 

  16. Liang YL, Lin SY, Brunicardi FC, et al. DNA damage response pathways in tumor suppression and cancer treatment. World J Surg 2009; 33: 661–6

    Article  PubMed  Google Scholar 

  17. Miwa M, Masutani M. PolyADP-ribosylation and cancer. Cancer Sci 2007; 98: 1528–35

    Article  PubMed  CAS  Google Scholar 

  18. Boyer-Chammard A, Taylor TH, Anton-Culver H. Survival differences in breast cancer among racial/ethnic groups: a population-based study. Cancer Detect Prev 1999; 23: 463–73

    Article  PubMed  CAS  Google Scholar 

  19. Gadgeel SM, Kalemkerian GP. Racial differences in lung cancer. Cancer Metastasis Rev 2003; 22: 39–46

    Article  PubMed  CAS  Google Scholar 

  20. Thatai LC, Banerjee M, Lai Z, et al. Racial disparity in clinical course and outcome of metastatic androgen-independent prostate cancer. Urology 2004; 64: 738–43

    Article  PubMed  Google Scholar 

  21. Lockett KL, Hall MC, Xu J, et al. The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function. Cancer Res 2004; 64: 6344–8

    Article  PubMed  CAS  Google Scholar 

  22. Zhang X, Miao X, Liang G, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65: 722–6

    PubMed  CAS  Google Scholar 

  23. Hao B, Wang H, Zhou K, et al. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res 2004; 64: 4378–84

    Article  PubMed  CAS  Google Scholar 

  24. Lee KH, Lee JH, Cho JK, et al. A prospective correlation of Lauren’s histological classification of stomach cancer with clinicopathological findings including DNA flow cytometry. Pathol Res Pract 2001; 197: 223–9

    Article  PubMed  CAS  Google Scholar 

  25. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001; 345: 784–9

    Article  PubMed  CAS  Google Scholar 

  26. Nossa CW, Jain P, Tamilselvam B, et al. Activation of the abundant nuclear factor poly(ADP-ribose) polymerase-1 by Helicobacter pylori. Proc Natl Acad Sci U S A 2009; 106: 19998–20003

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Wenting He and Tao Liu contributed equally to this work. This work was supported by the National Natural Science Foundation of China (project approval no. 30870364), Fundamental Research Funds for the Central Universities (project approval no. lzujbky-2010-207), and Research Funds of Lanzhou University Second Hospital (project approval no. YJ2010-14). The authors declare that they have no conflicts of interest relating to the content of this study.

Author information

Authors and Affiliations

  1. First Hospital of Lanzhou University, Lanzhou, Gansu Province, China

    Wenting He & Kexiang Zhu

  2. Key Laboratory of Digestive System Tumors, Lanzhou, Gansu Province, China

    Wenting He, Tao Liu, Yong Shan &  Yumin Li

  3. Second Hospital of Lanzhou University, Lanzhou, Gansu Province, China

    Tao Liu &  Yumin Li

Authors
  1. Wenting He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kexiang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yumin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yumin Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, W., Liu, T., Shan, Y. et al. PARP1 Polymorphisms Increase the Risk of Gastric Cancer in a Chinese Population. Mol Diagn Ther 16, 35–42 (2012). https://doi.org/10.1007/BF03256428

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256428

Keywords

Search

Navigation