Corelation of Homologous Recombination Repair System by Studying a Single-nucleotide Polymorphism in Xrcc3 Gene with Initiation and Progression of Colorectal Cancer

Document Type : Original Article (s)

Authors

1 Assistant Professor, Division of Genetics, Department of Biology, School of Sciences, The University of Isfahan, Isfahan, Iran.

2 Department of Biology, School of Sciences, The University of Isfahan, Isfahan, Iran.

3 Assistant Professor, Department of Oncology and Radiotherapy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

4 Assistant Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Background: Colorectal cancer is the third cause of cancer death in western countries. Age, inadequate diet, obesity, inactivity and genetic changes are some of the risk factors of colorectal cancer. Corelation of genetic diversity in homologous recombination repair system with cancer was evaluated in many recent studies. This study was done to investigate the correlation of T241M polymorphism in Xrcc3 gene and colorectal cancers.Methods: In this cross-sectional study after collecting blood samples and extraction genomic DNA, genotype distribution of the polymorphism was determined by RFLP-PCR (Restriction fragment lengh-polymerase-Polymerase chain reaction) method.Finding: A significant corelation between T241M polymorphism with colorectal cancer was seen. Age and family history were also corelated with this cancer. Although, there was no statistically relationship between smoking status and colon cancer, but it showed correlation with rectum cancer and it has been also observed that the most occurance of metastatic activity is in the rectum. Conclusion: According to our study T241M polymorphism in Xrcc3 gene from homologous recombination repair systm could be a suitable factor for early diagnosis of colorectal cancer especially rectum and its co-operation with smoking status. 

Keywords

References

  1. Markowitz SD, Bertagnolli MM. Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 2009; 361(25): 2449-60.
  2. Malekzadeh R, Bishehsari F, Mahdavinia M, Ansari R. Epidemiology and molecular genetics of colorectal cancer in iran: a review. Arch Iran Med 2009; 12(2): 161-9.
  3. Vogelstein B, Kinzler KW. The genetic basis of human cancer. 2nd ed. New York: McGraw-Hill Professional; 2002.
  4. Steineck G, Hagman U, Gerhardsson M, Norell SE. Vitamin A supplements, fried foods, fat and urothelial cancer. A case-referent study in Stockholm in 1985-87. Int J Cancer 1990; 45(6): 1006-11.
  5. Kune GA, Kune S, Watson LF. Body weight and physical activity as predictors of colorectal cancer risk. Nutr Cancer 1990; 13(1-2): 9-17.
  6. Klurfeld DM. Dietary fiber-mediated mechanisms in carcinogenesis. Cancer Res 1992; 52(7 Suppl): 2055s-9s.
  7. Khuhaprema T, Srivatanakul P. Colon and rectum cancer in Thailand: an overview. Jpn J Clin Oncol 2008; 38(4): 237-43.
  8. Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 1999; 340(3): 169-76.
  9. Blomqvist L, Holm T, Rubio C, Hindmarsh T. Rectal tumours--MR imaging with endorectal and/or phased-array coils, and histopathological staging on giant sections. A comparative study. Acta Radiol 1997; 38(3): 437-44.
  10. Weitz J, Koch M, Debus J, Hohler T, Galle PR, Buchler MW. Colorectal cancer. Lancet 2005; 365(9454): 153-65.
  11. Libutti SK, Saltz LB, Tepper JE. Colon cancer. In: DeVita VT, Lawrence TS, Rosenberg SA, Weinberg RA, DePinho RA, editors. DeVita, Hellman, and Rosenberg's cancer: principles & practice of oncology.Philadelphia: Lippincott Williams & Wilkins; 2008. p. 1232-84.
  12. Markowitz SD, Dawson DM, Willis J, Willson JK. Focus on colon cancer. Cancer Cell 2002; 1(3): 233-6.
  13. Compton C, Hawk ET, Grochow L, Lee F, Ritter M, Niederhuber JE. Colon cancer. In: Abeloff MD, Armitage JO, Niederhuber JE, editors. Abeloff's clinical oncology.London: Churchill Livingstone/Elsevier, 2008. p. 1477-534.
  14. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350(23): 2343-51.
  15. Gazelle GS, Gaa J, Saini S, Shellito P. Staging of colon carcinoma using water enema CT. J Comput Assist Tomogr 1995; 19(1): 87-91.
  16. Balthazar EJ, Megibow AJ, Hulnick D, Naidich DP. Carcinoma of the colon: detection and preoperative staging by CT. AJR Am J Roentgenol 1988; 150(2): 301-6.
  17. Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK. Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997. Arch Surg 1998; 133(8): 894-9.
  18. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61(5): 759-67.
  19. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998; 396(6712): 643-9.
  20. Kinzler KW, Vogelstein B. Landscaping the cancer terrain. Science 1998; 280(5366): 1036-7.
  21. Lindblom A. Different mechanisms in the tumorigenesis of proximal and distal colon cancers. Curr Opin Oncol 2001; 13(1): 63-9.
  22. de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, de Vries EG, Sijmons RH, et al. Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev 2002; 11(11): 1332-52.
  23. Houlston RS, Tomlinson IP. Polymorphisms and colorectal tumor risk. Gastroenterology 2001; 121(2): 282-301.
  24. Stoehlmacher J, Park DJ, Zhang W, Yang D, Groshen S, Zahedy S, et al. A multivariate analysis of genomic polymorphisms: prediction of clinical outcome to 5-FU/oxaliplatin combination chemotherapy in refractory colorectal cancer. Br J Cancer 2004; 91(2): 344-54.
  25. Liu N, Lamerdin JE, Tebbs RS, Schild D, Tucker JD, Shen MR, et al. XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Mol Cell 1998; 1(6): 783-93.
  26. Takata M, Sasaki MS, Tachiiri S, Fukushima T, Sonoda E, Schild D, et al. Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs. Mol Cell Biol 2001; 21(8): 2858-66.
  27. Ladiges W, Wiley J, MacAuley A. Polymorphisms in the DNA repair gene XRCC1 and age-related disease. Mech Ageing Dev 2003; 124(1): 27-32.
  28. Au WW, Salama SA, Sierra-Torres CH. Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 2003; 111(15): 1843-50.
  29. Gustincich S, Manfioletti G, Del Sal G, Schneider C, Carninci P. A fast method for high-quality genomic DNA extraction from whole human blood. Biotechniques 1991; 11(3): 298-300, 302.
Journal of Isfahan Medical School
Volume 29, Issue 137 - Serial Number 137
March and April 2011
Pages 518-525

Files

History

  • Receive Date: 10 June 2011
  • Revise Date:
  • Accept Date: 06 April 2022

Share

How to cite

Statistics