Detection of Polymorphisms of DNA Repair Genes (XRCC1 and XPC) in Prostate Cancer

DOI: 10.4236/jct.2013.410181   PDF   HTML     3,731 Downloads   4,783 Views   Citations


Prostate cancer is a common disease with a multifactorial and complex etiology. It is the most common male malignancy and the second leading cause of death in many countries. The widespread use of PSA testing has increased the detection of this cancer at earlier stages, although this diagnostic method has proved to be insufficient to identify the disease. DNA in most cells is regularly damaged by endogenous and exogenous mutagens. At least four main partially overlapping damage repair pathways operate in mammals. Common polymorphisms in DNA repair genes may alter protein function and an individual’s capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. In the present study, we investigated the genotypic distribution of XRCC1 and XPC polymorphisms and its association with prostate cancer risk, pathological staging and Gleason’s scoring. The present study was conducted in the departments of Clinical Pathology, Pathology, and Urology Faculty of Medicine, Alexandria University-Egypt. A total number of 50 patients with pathologically confirmed prostate cancer and 50 age-matched control subjects were enrolled in this study. The diagnosis was made on the basis of histopathological findings, following radical prostatectomy or transurethral resection of the prostate (TURP). Genomic DNA was extracted from peripheral blood using QIAamp blood DNA isolation kits. PCR followed by enzymatic digestion of the PCR products for (XRCC1, XPC) was used for the genotyping of these polymorphisms. Statistical analyses were performed using SPSS statistics version 20. The genotype frequencies of the studied polymorphisms in all the samples (n = 100), PC patients (n = 50) and healthy controls (n = 50) were consistent with the Hardy-Weinberg equilibrium distribution (p-value > 0.05). There was no statistical difference in the genotypes of the XRCC1 Arg399Gln and XPC Lys939Gln between cases and controls. The “Gln” allele frequency of XPC Lys939Gln as well as the “Gln” allele frequency of XRCC1 Arg399Gln tended to be lower in controls than in PC patients. Yet, these decreases were not statistically significant. We also examined the combined effect of XPC and XRCC1 and we found a decreased PC risk when XPC 939 Lys/Lys + Lys/Gln and XRCC1 399 Arg/Arg + Arg/Gln are combined (OR = 0.370, 95% CI = 0.142 - 0.962).

Share and Cite:

A. Sorour, I. Talaat, T. Youssif and M. Atta, "Detection of Polymorphisms of DNA Repair Genes (XRCC1 and XPC) in Prostate Cancer," Journal of Cancer Therapy, Vol. 4 No. 10, 2013, pp. 1499-1505. doi: 10.4236/jct.2013.410181.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] A. Jemal, R. Siegel, E. Ward, Y. Hao, J. Xu, T. Murray and M. J. Thun, “Cancer Statistics, 2008,” CA: A Cancer Journal for Clinicians, Vol. 58, No. 2, 2008, pp. 71-96. 2007.0010
[2] K. C. Chu, R. E. Tarone and H. P. Freeman, “Trends in Prostate Cancer Mortality among Black Men and White Men in the United States,” Cancer, Vol. 97, No. 6, 2003, pp. 1507-1516.
[3] A. W. Partin, M. W. Kattan, E. N. Subong, P. C. Walsh, K. J. Wojno, J. E. Oesterling, et al., “Combination of Prostate-Specific Antigen, Clinical Stage, and Gleason Score to Predict Pathological Stage of Localized Prostate Cancer. A Multi-Institutional Update,” JAMA, Vol. 277, No. 18, 1997, p. 1445.
[4] J. Xu, S. L. Zheng, A. Turner, et al., “Associations between hOGG1 Sequence Variants and Prostate Cancer Susceptibity,” Cancer Res, Vol. 62, No. 8, 2002, pp. 2253-2257.
[5] El Goode, C. M. Ulrich and J. D. Potter, “Polymorphisms in DNA Repair Genes and Associations with Cancer Risk,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 11, No. 12, 2002, pp. 1513-1530.
[6] M. C. Bosland, “Sex Steroids and Prostate Carcinogenesis: Integrated, Multifactorial Working Hypothesis,” Annals of the New York Academy of Sciences, Vol. 1089, No. 1, 2006, pp. 168-176.
[7] A. Van Hoffen, A. S. Balajee, A. A. van Zeeland and L. H. Mullenders, “Nucleotide Excision Repair and Its Interplay with Transcription,” Toxicology, Vol. 193, No. 1-2, 2003, pp. 79-90.
[8] Y. Kubotta, R. A. Nash, A. Klungland, et al., “Reconstitution of DNA Base Excision-Repair with Purified Human Proteins: Interaction between DNA Polymerase Beta and the XRCC1 Protein,” The EMBO Journal, Vol. 15, No. 23, 1996, pp. 6662-6670.
[9] D. M. Parkin, F. Bray, P. Ferlay and P. Pisani, “Global Cancer Statistics,” CA: A Cancer Journal for Clinicians, Vol. 55, No. 2, 2005, pp. 74-108.
[10] L. Li, C. Peterson and R. Legerski, “Sequence of the Mouse XPC cDNA and Genomic Structure of the Human XPC Gene,” Nucleic Acids Research, Vol. 24, No. 6, 1996, pp. 1026-1028.
[11] Y. Zhu, H. Yang, Q. Chen, J. Lin, H. B. Grossman, C. P. Dinney, X. Wu and J. Gu, “Modulation of DNA Damage/DNA Repair Capacity by XPC Polymorphisms,” DNA Repair (Amst), Vol. 7, No. 2, 2008, pp. 141-148.
[12] S. I. Berndt, E. A. Platz, M. D. Fallin, L. W. Thuita, S. C. Hoffman and K. J. Helzlsouer, “Genetic Variation in the Nucleotide Excision Repair Pathway and Colorectal Cancer Risk,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 15, No. 11, 2006, pp. 2263-2269.
[13] H. Shen, E. M. Sturgis, S. G. Khan, Y. Qiao, T. Shahlavi, S. A. Eicher, Y. Xu, X. Wang, S. S. Strom, M. R. Spitz, K. H. Kraemer and Q. Wei, “An Intronic Poly (AT) Polymorphism of the DNA Repair Gene XPC and Risk of Squamous Cell Carcinoma of the Head and Neck: A Case-Control Study,” Cancer Research, Vol. 61, 2001, pp. 3321-3325.
[14] S. Sanyal, F. Festa, S. Sakano, Z. Zhang, G. Steineck, U. Norming, H. Wijkstr?m, P. Larsson, R. Kumar and K. Hemminki, “Polymorphisms in DNA Repair and Metabolic Genes in Bladder Cancer,” Carcinogenesis, Vol. 25, No. 5, 2004, pp. 729-734.
[15] H. Sugisawa, R. Nakamura, I. Nakano and A. Sugisawa, “Four-Year Follow-Up Study of Self-Rated Health and Life Satisfaction among Caregivers,” Nihon Koshu Eisei Zasshi, Vol. 39, 1992, pp. 22-32.
[16] L. Fontana, R. Bosviel, L. Delort, L. Guy, N. Chalabi, F. Kwiatkowski, S. Satih, N. Rabiau, J. P. Boiteux, A. Chamoux, Y. J. Bignon and D. J. Bernard-Gallon, “DNA Repair Gene ERCC2, XPC, XRCC1, XRCC3 Polymorphisms and Associations with Bladder Cancer Risk in a French Cohort,” Anticancer Research, Vol. 28, No. 1, 2008, pp. 1853-1856.
[17] A. E. Vidal, S. Boiteux, I. D. Hickson, et al., “XRCC1 Coordinates the Initial and Late Stages of DNA Abasic Site Repair through Protein-Protein Interactions,” The EMBO Journal, Vol. 20, No. 22, 2001, pp. 6530-6539.
[18] J. D. Ritchey, W. Y. Huang, A. P. Chokkalingam, et al., “Genetic Variants of DNA Repair Genes and Prostate Cancer: A Population-Based Study,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 14, No. 7, 2005, pp. 1703-1709.
[19] G. H. van Gils, R. M. Bostick, M. C. Stern, et al., “Differences in Base Excision Repair Capacity May Modulate the Effect of Dietary Antioxidant Intake on Prostate Cancer Risk: An Example of Polymorphisms in the XRCC1 Gene,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 11, No. 11, 2002, pp. 1279-1284.
[20] B. A. Rybicki, D. V. Conti, A. Moreira, et al., “DNA Repair Gene XRCC1 and XPD Polymorphism and Risk of Prostate Cancer,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 13, No. 1, 2004, pp. 23-29.
[21] L. Chen, C. B. Ambrosone, J. Lee, et al., “Association between Polymorphisms in the DNA Repair Genes XRCC1 and APEX1, and the Risk of Prostate Cancer in White and Black Americans,” Journal of Urology, Vol. 175, No. 1, 2006, pp. 108-112.
[22] Z. Xu, L. X. Hua, L. X. Qian, et al., “Relationship between XRCC1 Polymorphisms and Susceptibility to Prostate Cancer in Men from Han, Southern China,” Asian Journal of Andrology, Vol. 9, No. 3, 2007, pp. 331-338.
[23] H. Hirata, Y. Hinoda, Y. Tanaka, N. Okayama, Y. Suehiro, K. Kawamoto, N. Kikuno, S. Majid, K. Vejdani and R. Dahiya, “Polymorphisma of DNA Repair Genes Are Risk Factors for Prostate Cancer,” European Journal of Cancer, Vol. 43, No. 2, 2007, pp. 231-237.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.