Advertisement

Tumor Biology

, Volume 37, Issue 5, pp 5905–5910 | Cite as

The relationship between five non-synonymous polymorphisms within three XRCC genes and gastric cancer risk in a Han Chinese population

  • Huansong Gong
  • He Li
  • Jing Zou
  • Jia Mi
  • Fang Liu
  • Dan Wang
  • Dong Yan
  • Bin Wang
  • Shuping Zhang
  • Geng Tian
Research Article

Abstract

We aimed to assess the association of five non-synonymous polymorphisms within three X-ray repair cross-complementing group (XRCC) genes with gastric cancer risk in Han Chinese. Genotyping was determined in 693 gastric cancer patients and 681 healthy controls. Statistical analyses were completed with SPSS (version 20.0) and Haplo.stats (version 1.6.11). The genotypes of XRCC1 gene rs25487 polymorphism (P = 0.003) differed significantly between patients and controls, even after the Bonferroni correction (P < 0.05/5), and this polymorphism was significantly associated with gastric cancer after adjusting for age, sex, body mass index, smoking, drinking, especially under a dominant model (odds ratio or OR; 95 % confidence interval or CI; P 1.59; 1.20–2.00; 0.001). In multiple-marker analysis, the most common allele combination was C-G-G-G-C (alleles in order of rs1799782, rs25489, rs25487, rs3218536, rs861539), which was overrepresented in controls relative to patients (adjusted simulated P = 0.0001). Contrastingly, the frequency of allele combination C-G-A-G-C was significantly higher in patients than in controls (adjusted simulated P = 0.0009), and this combination was associated with a strikingly increased risk of gastric cancer (OR; 95 % CI; P 2.39; 1.32–4.31; 0.0040) after the Bonferroni correction (P < 0.05/11) and adjusting for confounders. Our findings demonstrated that XRCC1 gene rs25487 polymorphism might play a leading role in pronounced susceptibility to gastric cancer in Han Chinese.

Keywords

Gastric cancer DNA repair system X-ray repair cross-complementing group Polymorphism Case-control association study 

Notes

Conflicts of interest

None

Supportive grants

This study was supported by Taishan Scholars Construction Engineering, National Natural Science Foundation of China (81400771 and 81171303), Shandong Provincial Natural Science Foundation (ZR2014HL028 and ZR2010HM091), A Project of Shandong Province Higher Educational Science and Technology Program (J14LE01), and Binzhou Medical University Scientific Research Funds (BY2013KYQD17 and BY2013KYQD18).

References

  1. 1.
    Alli E, Sharma VB, Sunderesakumar P, Ford JM. Defective repair of oxidative dna damage in triple-negative breast cancer confers sensitivity to inhibition of poly(adp-ribose) polymerase. Cancer Res. 2009;69:3589–96.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Orlow I, Park BJ, Mujumdar U, Patel H, Siu-Lau P, Clas BA, et al. DNA damage and repair capacity in patients with lung cancer: prediction of multiple primary tumors. J Clin Oncol. 2008;26:3560–6.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Aggarwal M, Brosh Jr RM. Functional analyses of human DNA repair proteins important for aging and genomic stability using yeast genetics. DNA Repair (Amst). 2012;11:335–48.CrossRefGoogle Scholar
  4. 4.
    Babron MC, Kazma R, Gaborieau V, McKay J, Brennan P, Sarasin A, et al. Genetic variants in DNA repair pathways and risk of upper aerodigestive tract cancers: combined analysis of data from two genome-wide association studies in European populations. Carcinogenesis. 2014;35:1523–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Dizdaroglu M. Oxidatively induced DNA damage and its repair in cancer. Mutat Res Rev Mutat Res. 2015;763:212–45.CrossRefPubMedGoogle Scholar
  6. 6.
    Qiao W, Wang T, Zhang L, Tang Q, Wang D, Sun H. Association study of single nucleotide polymorphisms in xrcc1 gene with the risk of gastric cancer in Chinese population. Int J Biol Sci. 2013;9:753–8.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Zhao DY, Cheng L, Yu J, Shen H. Xrcc1 genetic polymorphism arg339gln, arg194trp, arg280his and gastric cancer risk: an evidence based decision. Cancer Biomark. 2014;14:449–56.CrossRefPubMedGoogle Scholar
  8. 8.
    Perez LO, Crivaro A, Barbisan G, Poleri L, Golijow CD. Xrcc2 r188h (rs3218536), xrcc3 t241m (rs861539) and r243h (rs77381814) single nucleotide polymorphisms in cervical cancer risk. Pathol Oncol Res. 2013;19:553–8.CrossRefPubMedGoogle Scholar
  9. 9.
    Curtin K, Lin WY, George R, Katory M, Shorto J, Cannon-Albright LA, et al. Genetic variants in xrcc2: new insights into colorectal cancer tumorigenesis. Cancer Epidemiol Biomarkers Prev. 2009;18:2476–84.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Qin XP, Zhou Y, Chen Y, Li NN, Wu XT. Xrcc3 thr241met polymorphism and gastric cancer susceptibility: a meta-analysis. Clin Res Hepatol Gastroenterol. 2014;38:226–34.CrossRefPubMedGoogle Scholar
  11. 11.
    McLean MH, El-Omar EM. Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol. 2014;11:664–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ Res. 2001;88:733–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of ld and haplotype maps. Bioinformatics. 2005;21:263–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Yang TP, Beazley C, Montgomery SB, Dimas AS, Gutierrez-Arcelus M, Stranger BE, et al. Genevar: a database and java application for the analysis and visualization of snp-gene associations in eqtl studies. Bioinformatics. 2010;26:2474–6.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Gok I, Baday M, Cetinkunar S, Kilic K, Bilgin BC. Polymorphisms in DNA repair genes xrcc2 and xrcc3 risk of gastric cancer in Turkey. Bosn J Basic Med Sci. 2014;14:214–8.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wang Z, Chen X, Liu B, Li S, Liu M, Xue H. Quantitative assessment of the associations between DNA repair gene xrcc3 thr241met polymorphism and gastric cancer. Tumour Biol. 2014;35:1589–98.CrossRefPubMedGoogle Scholar
  17. 17.
    Lee SG, Kim B, Choi J, Kim C, Lee I, Song K. Genetic polymorphisms of xrcc1 and risk of gastric cancer. Cancer Lett. 2002;187:53–60.CrossRefPubMedGoogle Scholar
  18. 18.
    Abdel-Rahman O. Hedgehog pathway aberrations and gastric cancer; evaluation of prognostic impact and exploration of therapeutic potentials. Tumour Biol. 2015;36:1367–74.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhou J, Liu ZY, Li CB, Gao S, Ding LH, Wu XL, et al. Genetic polymorphisms of DNA repair pathways influence the response to chemotherapy and overall survival of gastric cancer. Tumour Biol. 2015;36:3017–23.CrossRefPubMedGoogle Scholar
  20. 20.
    Boerner JL, Nechiporchik N, Mueller KL, Polin L, Heilbrun L, Boerner SA, et al. Protein expression of DNA damage repair proteins dictates response to topoisomerase and PARP inhibitors in triple-negative breast cancer. PLoS ONE. 2015;10:e0119614.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Sarangi P, Zhao X. Sumo-mediated regulation of DNA damage repair and responses. Trends Biochem Sci. 2015;40:233–42.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kim HM, Colaiacovo MP. New insights into the post-translational regulation of DNA damage response and double-strand break repair in caenorhabditis elegans. Genetics. 2015.Google Scholar
  23. 23.
    Dong H, Shi Q, Song X, Fu J, Hu L, Xu D, Su C, Xia X, Song E, Song Y. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: the activations of nhej, ber and ner via atm-p53 signaling axis. Toxicol Appl Pharmacol. 2015.Google Scholar
  24. 24.
    Niu W, Qi Y, Hou S, Zhai X, Zhou W, Qiu C. Haplotype-based association of the renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: The Fangshan Study. J Hypertens. 2009;27:1384–91.CrossRefPubMedGoogle Scholar
  25. 25.
    Bugawan TL, Angelini G, Larrick J, Auricchio S, Ferrara GB, Erlich HA. A combination of a particular hla-dp beta allele and an hla-dq heterodimer confers susceptibility to coeliac disease. Nature. 1989;339:470–3.CrossRefPubMedGoogle Scholar
  26. 26.
    Gai LP, Liu H, Cui JH, Ji N, Ding XD, Sun C, et al. Distributions of allele combination in single and cross loci among patients with several kinds of chronic diseases and the normal population. Genomics. 2015;105:168–74.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Gastric and Intestine DepartmentYantai Affiliated Hospital of Binzhou Medical UniversityYantaiChina
  2. 2.Department of RadiologyYantai Affiliated Hospital of Binzhou Medical UniversityYantaiChina
  3. 3.Medicine and Pharmacy Research CenterBinzhou Medical UniversityYantaiChina
  4. 4.Institute of Molecular ImagingBinzhou Medical UniversityYantaiChina
  5. 5.Institute of PharmacologyBinzhou Medical UniversityYantaiChina

Personalised recommendations