Skip to main content

Advertisement

Log in

Association of mtDNA D-Loop Polymorphisms with Risk of Gastric Cancer in Chinese Population

  • Research
  • Published:
Pathology & Oncology Research

Abstract

The aim of present study was to evaluate the association of common polymorphisms detected in mitochondrial DNA (mtDNA) D-loop region (mononucleotide repetitive D310, single nucleotide polymorphism (SNP) D16521) with susceptibility to gastric cancer (GC) in northwestern Chinese population. A total of 180 GC patients and 218 healthy controls were investigated by using PCR- denaturing high performance liquid chromatography (DHPLC) assay. Genotype and allele distributions and haplotype construction were analyzed in case–control study. We found D310 and D16521 heteroplasmy were significantly different between GC cases and controls (p < 0.05), and D16521 homoplasmy showed association with histological grade of GC (p < 0.05). Haplotype 7C/T, 8C/C and 9C/C had significant association with GC risk implied from analysis of D310 and D16521. Taken together, these findings suggested that mtDNA D-Loop polymorphisms and haplotypes may contribute to genetic susceptibility to GC in Chinese population.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

GC:

Gastric cancer

MtDNA:

Mitochondrial DNA

SNP:

Single nucleotide polymorphism

D310:

Polytract of cytosines at nucleotide 310 in the mitochondrial genome

DHPLC:

Denaturing high performance liquid chromatography

References

  1. Sun XD, Mu R, Zhou YS, Dai XD, Zhang SW, Lu FZ, Qiao YL et al (2004) Analysis of mortality rate of stomach caner and its trend in twenty years in China. (Article in Chinese). Zhonghua Zhong Liu Za Zhi 26(1):4–9

    PubMed  CAS  Google Scholar 

  2. Parkin DM, Bray F, Ferlay J, Pisani P (2005) Global cancer statistics, 2002. CA Cancer J Clin 55:74–108

    Article  PubMed  Google Scholar 

  3. Stadtlander CT, Waterbor J (1999) Molecular epidemiology pathogenesis and prevention of gastric cancer. Carcinogenesis 20:2195–2207

    Article  PubMed  CAS  Google Scholar 

  4. Barber M, Fitzgerald RC, Caldas C (2006) Familial gastric cancer—aetiology and pathogenesis. Best Pract Res Clin Gastroenterol 207:21–34

    Google Scholar 

  5. Brenner C, Kroemer G (2000) Apoptosis, mitochondria, the death signal integrators. Science 289:1150–1151

    Article  PubMed  CAS  Google Scholar 

  6. Modica-Napolitano JS, Kulaviec M, Singh KK (2007) Mitochondria and human cancer. Curr Mol Med 7:121–131

    Article  PubMed  CAS  Google Scholar 

  7. Fliss MS, Usadel H, Caballero OL, Wu L, Buta MR, Eleff SM et al (2000) Facile detection of mitochondrial DNA mutations in tumors and bodily fluids. Science 287:2017–2019

    Article  PubMed  CAS  Google Scholar 

  8. Parr RL, Dakubo GD, Thayer RE, McKenney K, Birch-Machin MA (2006) Mitochondrial DNA as a potential tool for early cancer detection. Hum Genomics 24:252–257

    Google Scholar 

  9. Michikawa Y, Mazzucchelli F, Bresolin N et al (1999) Aging dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286:774–779

    Article  PubMed  CAS  Google Scholar 

  10. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (1999) Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet 23:147

    Article  PubMed  CAS  Google Scholar 

  11. Tamura G, Nishizuka S, Maesawa C, Suzuki Y, Iwaya T, Sakata K, Endoh YT, Motoyama T (1999) Mutations in mitochondrial control region DNA in gastric tumors of Japanese patients. Eur J Cancer 35:316–319

    Article  PubMed  CAS  Google Scholar 

  12. Han CB, Li F, Zhao YJ, Ma JM, Wu DY, Zhang YK, Xin Y (2003) Variations of mitochondrial D-loop region plus downstream gene 12S rRNA-tRNAPhe and gastric carcinomas. World J Gastroenterol 9:1925–1929

    PubMed  CAS  Google Scholar 

  13. Wu CW, Yin PH, Hung WY, Li AFY, Li SH, Chi CW, Wei YH, Lee HC (2005) Mitochondrial DNA mutations and mitochondrial DNA depletion in gastric cancer. Genes Chromosom Cancer 44:19–28

    Article  PubMed  CAS  Google Scholar 

  14. Sanchez-Cespedes M, Parrella P, Nomoto S, Cohen D, Xiao Y, Esteller M, Jeronimo C, Jordan RC, Nicol T, Koch WM, Schoenberg M, Mazzarelli P et al (2001) Identification of a mononucleotide repeat as a major target for mitochondrial DNA alterations in human tumors. Cancer Res 61:7015–7019

    PubMed  CAS  Google Scholar 

  15. Lee HC, Yin PH, Lin JC, Wu CC, Chen CY, Wu CW, Chi CW, Tam TN, Wei YH (2005) Mitochondrial genome instability and mtDNA depletion in human cancers. Ann NY Acad Sci 1042:109–122

    Article  PubMed  CAS  Google Scholar 

  16. Schwartz S Jr, Alazzouzi H, Perucho M (2006) Mutational dynamic in human tumors confirms the neutral intrinsic instability of the mitochondrial D-loop polycytidine repeat. Genes Chromosom Cancer 45:770–780

    Article  PubMed  CAS  Google Scholar 

  17. Kose K, Hiyama T, Tanaka S, Yoshihara M, Yasui W, Chayama K (2005) Somatic mutations of mitochondrial DNA in digestive tract cancers. J Gastroenterol Hepatol 20:1679–1684

    Article  PubMed  CAS  Google Scholar 

  18. Chang S-C, Lin P-C, Yang S-H, Wang H-S, Liang W-Y, Lin J-K (2009) Mitochondrial D-loop mutation is a common event in colorectal cancers with p53 mutations. Int J Colorectal Dis 24:623–628

    Article  PubMed  Google Scholar 

  19. Saccone C, Attimonelli M, Sibs E (1987) Structural elements highly preserved during the evolution of the D-Loop region in vertebrate mitochondrial DNA. J Mol Evol 26:205–211

    Article  PubMed  CAS  Google Scholar 

  20. Pesole G, Gissi C, De Chirico A, Saccone C (1999) Nucleotide substitution rate of mammalian mitochondrial genomes. J Mol Evol 48:427–434

    Article  PubMed  CAS  Google Scholar 

  21. Montoya J, López-Gallardo E, Díez-Sánchez C, López-Pérez MJ (2009) 20 years of human mtDNA pathologic point mutations: carefully reading the pathogenicity criteria. Biochim Biophys Acta 1787:476–483

    Article  PubMed  CAS  Google Scholar 

  22. Solaini ER-PG, Harris DA, Lenaz G, Sgarbi G, Baracca A (2008) The study of the pathogenic mechanism of mitochondrial diseases provides information on basic bioenergetics. Biochim Biophys Acta 1777:941–945

    Article  PubMed  CAS  Google Scholar 

  23. Anderson S, Bankier AT, Barrel BG, De Bruijn MHL, Coulson AR, Drouin J, Eperson IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    Article  PubMed  CAS  Google Scholar 

  24. Broder AC (1925) The grading of carcinoma. Minn Med 8:726–730

    Google Scholar 

  25. Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98

    Article  PubMed  CAS  Google Scholar 

  26. Habano W, Sugai T, Nakamura SI et al (2000) Microsatellite instability and mutation of mitochondrial and nuclear DNA in gastric carcinoma. Gastroenterology 118:835–841

    Article  PubMed  CAS  Google Scholar 

  27. Mambo E, Chatterjee A, Xing M et al (2005) Tumor-specific changes in mtDNA content in human cancer. Int J Cancer 116:920–924

    Article  PubMed  CAS  Google Scholar 

  28. Sbisà E, Tanzariello R, Reyes A, Pesole G, Saccone C (1997) Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications. Gene 205:125–140

    Article  PubMed  Google Scholar 

  29. Pham XH, Farge G, Shi Y, Gaspari M, Gustafsson CM, Falkenberg M (2006) Conserved sequence box II directs transcription terminationand primer formation in mitochondria. J Biol Chem 281:647–652

    Article  Google Scholar 

  30. Bandy B, Davison AJ (1990) Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med 8:523–539

    Article  PubMed  CAS  Google Scholar 

  31. Chinnery PF, Samuels DC, Elson J, Turnbull DM (2002) Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism? Lancet 360:1323–1325

    Article  PubMed  CAS  Google Scholar 

  32. Verma M, Kumar D (2007) Application of mitochondrial genome information in cancer epidemiology. Clin Chim Acta 383:41–50

    Article  PubMed  CAS  Google Scholar 

  33. Modica-Napolitano JS, Singh KK (2002) Mitochondria as targets for detection and treatment of cancer. Expert Rev Mol Med, Cambridge University Press, pp 1–19

  34. Biggin A, Henke R, Bennetts B, Thorburn DR, Christodoulou J (2005) Mutation screening of the mitochondrial genome using denaturing high-performance liquid chromatography. Mol Genet Metab 84:61–74

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We express our appreciation to the original DNA donors who made this study possible. This work was supported by a grant from Natural Science Foundation of Gansu province (0710RJZA017), Key Technologies R&D Program (0708NKCA096) from the Gansu Provincial Science and Technology Committee, China, grant of Platform of Genetic Resource of Chinese Project, from the Ministry of Science and Technology PR China (2006DKA21301), and Program for New Century Excellent Talents in University, from the Ministry of Education of PR China (NCET-05-0885), National Natural Science Foundation of China (81071701), and State Key Development Program of Basic Research of China (2010CB834201).

Conflicts of interest

No conflicts of interest were declared in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Feng Gao or Xiao-dong Xie.

Additional information

Li Wei and Yong Zhao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wei, L., Zhao, Y., Guo, Tk. et al. Association of mtDNA D-Loop Polymorphisms with Risk of Gastric Cancer in Chinese Population. Pathol. Oncol. Res. 17, 735–742 (2011). https://doi.org/10.1007/s12253-011-9378-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-011-9378-7

Keywords

Navigation