Abstract
The genes involved in DNA repair system play a crucial role in the protection against mutations. It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer (BC). The aim of the present study was to evaluate the association of genetic polymorphisms in 2 DNA repair genes, XPD (Asp312Asn) and XRCC1 (A399G), with BC susceptibility. We further investigated the potential combined effect of these DNA repair variants on BC risk. Both XPD (xeroderma pigmentosum group D) and XRCC1 (X-ray repair cross-complementing group 1) polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study. Our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the BC patients than in the normal individuals (P ≤ 0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing BC. Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease. Finally, the combination of AA(XPD) + AG(XRCC1) were significantly associated with BC risk. Our results suggested that, XPD gene is an important candidate gene for susceptibility to BC. Also, gene–gene interaction between XPD(AA) + XRCC1(AG) polymorphism may be associated with increased risk of BC in Egyptian women.
Similar content being viewed by others
References
Parkin DM, Bray F, Ferlay J (2005) Global cancer statistics. CA Cancer J Clin 55:74–108
Ibrahim AS et al (2002) Cancer profile in Gharbiah, Egypt: methodology and results. Ministry of Health and Population Egypt and Middle East Cancer Consortium, Cairo
Elatar I (2001) Cancer registration NCI, Egypt, Cairo. National Cancer Institute, Egypt
Hosny G, Elkaffas SM (2002) A prediction model for the incidence patterns of female breast cancers in Alexandria, Egypt. J Egypt Public Health Assoc 77(3–4):329–345
Hu JJ, Smith TR, Miller MS, Lohman K, Case LD (2002) Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ Mol Mutagen 39:208–215
Parshad R, Price FM, Bohr VA, Cowans KH, Zujewski JA, Sanford KK (1996) Deficient DNA repair capacity, a predisposing factor in breast cancer. Br J Cancer 74(1):1–5
Debniak T, Scott RJ, Huzarski T, Byrski T, Masojc B, van de Wetering T, Serrano-Fernandez P, Gorski B, Cybulski C, Gronwald J, Debniak B, Maleszka R, Kladny J, Bieniek A, Nagay L, Haus O, Grzybowska E, Wandzel P, Niepsuj S, Narod SA, Lubinski J (2006) XPD common variants and their association with melanoma and breast cancer risk. Breast Cancer Res Treat 98:209–215
de Boer JG (2002) Polymorphisms in DNA repair and environmental interactions. Mutat Res 509:201–210
Berwick M, Vineis P (2000) Markers of DNA repair and susceptibility to cancer in humans: an epidemiologic review. J Natl Cancer Inst 92:874–897
Laine JP, Mocquet V, Bonfanti M, Braun C, Egly JM, Brousset P (2007) Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair (Amst) 6:1264–1270
Shen MR, Jones IM, Mohrenweiser H (1998) Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer Res 58:604–608
Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21:551–555
Caldecott KW, Aoufouchi S, Johnson P, Shall S (1996) XRCC1 polypeptide interacts with DNA polymerase beta and possibly poly(ADP-ribose) polymerase, and DNA ligase III is a novel molecular ‘nick-sensor’ in vitro. Nucleic Acids Res 24:4387–4394
Hu JJ, Mohrenweiser HW, Bell DA (2002) Symposium overview: genetic polymorphisms in DNA repair and cancer risk. Toxicol Appl Pharmacol 185:64–73
Bloom HI, Richardson WW (1957) Histological grading and prognosis. Br J Cancer 11:359–377
Breast AJCC (2002) Cancer staging manual. In: American Joint Committee on Cancer, 6th ed. Springer, New York, pp 171–180
Rybicki BA, Conti DV, Moreira A, Cicek M, Casey G, Witte JS (2004) Repair gene XRCC1 and XPD polymorphisms and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 13:23–29
Ito H, Matsuo K, Hamajima N, Mitsudomi T (2004) Gene–environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis 25(8):1395–1401
Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ (2004) Cancer statistics. CA Cancer J Clin 54:8–29
Helzlsouer KJ, Harris EL, Parshad R (1996) DNA repair proficiency: potential susceptibility factor for breast cancer. J Natl Cancer Inst 88:754–755
Jyothish B, Ankathil R, Chandini R et al (1998) DNA repair proficiency: a potential marker for identification of high risk members in breast cancer families. Cancer Lett 124:9–13
Matullo G, Palli D, Peluso M et al (2001) XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 22:1437–1445
Clarkson SG, Wood RD (2005) Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal. DNA Repair (Amst) 4:1068–1074
Pachkowski BF, Winkel S, Kubota Y et al (2006) XRCC1 genotype and breast cancer: functional studies and epidemiologic data show interactions between XRCC1 codon 280 His and smoking. Cancer Res 66:2860–2868
Zhang L, Zhang Z, Yan W (2005) Single nucleotide polymorphisms for DNA repair genes in breast cancer patients. Clin Chim Acta 359:150–155
Wang HC, Liu CS, Wang HC, Tsai RY, Tsai CW, Wang RF, Chen YS, Chiu CF, Bau DT, Huang CY (2010) Significant association of XPD Asp312Asn polymorphism with breast cancer in Taiwanese patients. Chin J Physiol 53 (prepublication ahead of print)
Bernard-Gallon D, Bosviel R, Delort L, Fontana L, Chamoux A, Rabiau N, Kwiatkowski F, Chalabi N, Satih S, Bignon YJ (2008) DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk. Mol Cancer 7:36
Kuschel B, Chenevix-Trench G, Spurdle AB, Chen X, Hopper JL, Giles GG, McCredie M, Chang-Claude J, Gregory CS, Day NE, Easton DF, Ponder BA, Dunning AM, Pharoah PD (2005) Common polymorphisms in ERCC2 (Xeroderma pigmentosum D) are not associated with breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:1828–1831
Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ (2008) Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis 29:2132–2138
Figueiredo JC, Knight JA, Briollais L et al (2004) Polymorphisms XRCC1–R399Q and XRCC3–T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev 13:583–591
Shu XO, Cai Q, Gao YT et al (2003) A population-based case control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 12:1462–1467
Smith TR, Miller MS, Lohman K et al (2003) Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer Lett 190:183–190
Deligezer U, Dalay N (2004) Association of the XRCC1 gene polymorphisms with cancer risk in Turkish breast cancer patients. Exp Mol Med 36:572–575
Shen J, Gammon MD, Terry MB et al (2005) Polymorphisms in XRCC1 modify the association between polycyclic aromatic hydrocarbon-DNA adducts, cigarette smoking, dietary antioxidants, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:336–342
Chacko P, Rajan B, Joseph T et al (2005) Polymorphisms in DNA repair gene XRCC1 and increased genetic susceptibility to breast cancer. Breast Cancer Res Treat 89:15–21
Syamala VS, Syamala V, Sreedharan H, Raveendran PB, Kuttan R, Ankathil R (2009) Contribution of XPD (Lys751Gln) and XRCC1 (Arg399Gln) polymorphisms in familial and sporadic breast cancer predisposition and survival: an Indian report. Pathol Oncol Res 15:389–397
Duell EJ, Millikan RC, Pittman GS et al (2001) Polymorphisms in the DNA repair gene XRCC1 and breast cancer. Cancer Epidemiol Biomarkers Prev 10:217–222
Kim SU, Park SK, Yoo KY et al (2002) XRCC1 genetic polymorphism and breast cancer risk. Pharmacogenetics 12:335–338
Clarkson SG, Wood RD (2005) Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal. DNA Repair (Amst) 4:1068–1074
Wang Y, Spitz MR, Zhu Y et al (2003) From genotype to phenotype: correlating XRCC1 polymorphisms with mutagen sensitivity. DNA Repair (Amst) 2:901–908
Zipprich J, Terry MB, Brandt-Rauf P, Freyer GA, Liao Y, Agrawal M, Gurvich I, Senie R, Santella RM (2010) XRCC1 polymorphisms and breast cancer risk from the New York Site of the Breast Cancer Family Registry: a family-based case-control study. J Carcinog 9:4
Matullo G, Palli D, Peluso M et al (2001) XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 22:1437–1445
Lunn RM, Langlois RG, Hsieh LL et al (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 59:2557–2561
Hu JJ, Smith TR, Miller MS et al (2001) Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis 22:917–922
Acknowledgments
This study was funded with the support of academic research in Zagazig University Projects, Zagazig University. Postgraduate and Research Affairs.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hussien, Y.M., Gharib, A.F., Awad, H.A. et al. Impact of DNA repair genes polymorphism (XPD and XRCC1) on the risk of breast cancer in Egyptian female patients. Mol Biol Rep 39, 1895–1901 (2012). https://doi.org/10.1007/s11033-011-0935-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11033-011-0935-7