Genetic Variation in a DNA Double Strand Break Repair Gene in Saudi Population: A Comparative Study with Worldwide Ethnic Groups

  • Published : 2013.12.31


DNA repair capacity is crucial in maintaining cellular functions and homeostasis. However, it can be altered based on DNA sequence variations in DNA repair genes and this may lead to the development of many diseases including malignancies. Identification of genetic polymorphisms responsible for reduced DNA repair capacity is necessary for better prevention. Homologous recombination (HR), a major double strand break repair pathway, plays a critical role in maintaining the genome stability. The present study was performed to determine the frequency of the HR gene XRCC3 Exon 7 (C18067T, rs861539) polymorphisms in Saudi Arabian population in comparison with epidemiological studies by "MEDLINE" search to equate with global populations. The variant allelic (T) frequency of XRCC3 (C>T) was found to be 39%. Our results suggest that frequency of XRCC3 (C>T) DNA repair gene exhibits distinctive patterns compared with the Saudi Arabian population and this might be attributed to ethnic variation. The present findings may help in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.


  1. Al-Hadyan KS, Al-Harbi NM, Al-Qahtani SS, Alsbeih GA, (2012). Involvement of single-nucleotide polymorphisms in predisposition to head and neck cancer in Saudi Arabia. Genet Test Mol Biomarkers. 16, 95-01.
  2. Au WW, Navasumrit P, Ruchirawat M (2004). Use of biomarkers to characterize functions of polymorphic DNA repair genotypes. Int J Hyg Environ Health, 207, 301-13.
  3. Casson AG, Zheng Z, Evans SC, et al (2005). Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. Carcinogenesis, 26, 1536-41.
  4. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003). Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J, 17, 1195-214.
  5. Dhillon VS, Yeoh E, Fenech M, (2011). DNA repair gene polymorphisms and prostate cancer risk in South Australia--results of a pilot study. Urol Oncol, 29, 641-46.
  6. Fabiani E, D'Alo F, Scardocci A, et al (2009). Polymorphisms of detoxification and DNA repair enzymes in myelodyplastic syndromes. Leuk Res, 33, 1068-71.
  7. Griffin CS (2002). Aneuploidy, centrosome activity and chromosome instability in cells deficient in homologous recombination repair. Mutat Res, 504, 149-55.
  8. Hu JJ, Mohrenweiser HW, Bell DA, et al (2002). Symposium overview: genetic polymorphisms in DNA repair and cancer risk. Toxicol Appl Pharmacol, 185, 64-73.
  9. Jackson SP, Bartek J (2009). The DNA-damage response in human biology and disease. Nature, 461, 1071-78.
  10. Jackson S (2002). Sensing and repairing DNA double-strand breaks. Carcinogenesis, 23, 687-96.
  11. Joksic G, Petrovic S, Joksic I, Leskovac A (2009). Biological effects of Echinacea purpurea on human blood cells. Arh Hig Rada Toksikol, 60, 165-72.
  12. Kaur TB, Travaline JM, Gaugan JP et al (2000) Role of polymorphisms in codons 143 and 160 of the O6-alkylguanine DNA alkyl transferase gene in lung cancer risk. Cancer Epidemiol Biomarkers Prev, 9, 339-42.
  13. Karagiannis TC, El-Osta A, (2004). Double-strand breaks: signalling pathways and repair mechanisms. Cell Mol Life Sci. 61, 2137-47.
  14. Kittles RA, Weiss KM, (2003). Race, ancestry, and genes: implications for defining disease risk. Annu Rev Genomics Hum Genet, 4, 33-67.
  15. Kietthubthew S, Sriplung H, Au WW, Ishida T, (2006). Polymorphism in DNA repair genes and oral squamous cell carcinoma in Thailand. Int J Hyg Environ Health, 209, 21-9.
  16. Kiyohara C, Horiuchi T, Takayama K, Nakanishi Y, (2012). Genetic polymorphisms involved in carcinogen metabolism and DNA repair and lung cancer risk in a Japanese population. J Thorac Oncol, 7, 954-62.
  17. Lindahl T, Barnes DE, (2000). Repair of endogenous DNA damage. Cold Spring Harb Symp Quant Biol, 65, 127-33.
  18. Lopez-Cima MF, González-Arriaga P, Garcia-Castro L, et al (2007). Polymorphisms in XPC, XPD, XRCC1, and XRCC3 DNA repair genes and lung cancer risk in a population of northern Spain. BMC Cancer, 7, 162.
  19. Mandal RK, Mittal T, Kapoor R, Mittal RD, (2010). NER and BER repair gene polymorphisms in a healthy north Indian cohort and comparison with different ethnic groups worldwide. Asian Pac J Cancer Prev, 11, 1601-4.
  20. Mandal RK, Kapoor R, Mittal RD, (2010). Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. DNA Cell Biol, 29, 669-74.
  21. Matullo G, Guarrera S, Sacerdote C, et al (2005). Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study. Cancer Epidemiol Biomarkers Prev, 14, 2569-78.
  22. Misra RR, Ratnasinghe D, Tangrea JA, et al (2003). Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett, 191, 171-8.
  23. Mittal RD, Gangwar R, Mandal RK, Srivastava P, Ahirwar DK (2012). Gene variants of XRCC4 and XRCC3 and their association with risk for urothelial bladder cancer. Mol Biol Rep, 39, 1667-75.
  24. Mohrenweiser HW, Wilson DM, Jones IM, (2003). Challenges and complexities in estimating both the functional impact and disease risk associated with the extensive genetic variation in human DNA repair genes. Mutat Res, 526, 93-125.
  25. Popanda O, Schattenberg T, Phong CT, et al. (2004). Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis, 25, 2433-41.
  26. Qian B, Zhang H, Zhang L, et al (2011). Association of genetic polymorphisms in DNA repair pathway genes with nonsmall cell lung cancer risk. Lung Cancer, 73, 138-46.
  27. Schantz SP, Hsu TC, Ainslie N, et al (1989). Young adults with head and neck cancer express increased susceptibility to mutagen-induced chromosome damage. JAMA, 26, 3313-15.
  28. Shen MR, Jones IM, Mohrenweiser H (1998). Non-conservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res, 58, 604-60.
  29. Sliwinski T, Walczak A, Przybylowska K, et al (2010). Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population. Exp Mol Pathol, 89, 358-66.
  30. Synowiec E, Stefanska J, Morawiec Z, Blasiak J, Wozniak K, (2008). Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mutat Res, 648, 65-72.
  31. Takata M, Sasaki MS, Sonoda E, et al (1998). Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. Embo J, 17, 5497-508.
  32. Tebbs RS, Zhao Y, Tucker JD, et al (1995). Scheerer JB, Siciliano MJ, Hwang M, Liu N, Legerski RJ, Thompson LH. Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc Natl Acad Sci U S A, 92, 6354-8.
  33. Thompson LH, Schild D (2001). Homologous recombinational repair of DNA ensures mammalian chromosome stability. Mutat Res, 477, 131-53.
  34. Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N (2004). Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst, 96, 434-42.
  35. Wang LE, Sturgis EM, Eicher SA, et al (1998). Mutagen sensitivity to benzo(a)pyrene diol epoxide and the risk of squamous cell carcinoma of the head and neck. Clin Cancer Res, 4, 1773-78.

Cited by

  1. Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan vol.15, pp.23, 2015,
  2. Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met Gene Polymorphisms with Increased Risk of Head and Neck Cancer vol.15, pp.23, 2015,
  3. Molecular Links between Alcohol and Tobacco Induced DNA Damage, Gene Polymorphisms and Patho-physiological Consequences: A Systematic Review of Hepatic Carcinogenesis vol.16, pp.12, 2015,
  4. Association of DNA repair genes polymorphisms and mutations with increased risk of head and neck cancer: a review vol.34, pp.12, 2017,