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Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India

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Tumor Biology

Abstract

Squamous cell carcinoma of head and neck (SCCHN) is the sixth most common cancer globally, and in India, it accounts for 30% of all cancer cases. Epidemiological studies have shown a positive association between defective DNA repair capacity and SCCHN. The underlying mechanism of their involvement is not well understood. In the present study, we have analyzed the relationship between SCCHN and the expression of DNA repair genes namely X-ray repair cross-complementing group 1 (XRCC1), xeroderma pigmentosum group D (XPD), and 8-oxoguanine DNA glycosylase (OGG1) in 75 SCCHN cases and equal number of matched healthy controls. Additionally, levels of DNA adduct [8-hydroxyguanine (8-OHdG)] in 45 SCCHN cases and 45 healthy controls were also determined, to ascertain a link between mRNA expression of these three genes and DNA adducts. The relative expression of XRCC1, XPD, and OGG1 in head and neck cancer patients was found to be significantly low as compared to controls. The percent difference of mean relative expression between cases and controls demonstrated maximum lowering in OGG1 (47.3%) > XPD (30.7%) > XRCC1 (25.2%). A negative Spearmen correlation between XRCC1 vs. 8-OHdG in cases was observed. In multivariate logistic regression analysis (adjusting for age, gender, smoking status, and alcohol use), low expression of XRCC1, XPD, and OGG1 was associated with a statistically significant increased risk of SCCHN [crude odds ratios (ORs) (95%CI) OR 2.10; (1.06–4.17), OR 2.76; (1.39–5.49), and 5.24 (2.38–11.52), respectively]. In conclusion, our study demonstrated that reduced expression of XRCC1, XPD, and OGG1 is associated with more than twofold increased risk in SCCHN.

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References

  1. Hartwell LH, Weinert TA. Checkpoints: controls that ensure the order of cell cycle events. Science. 1989;246:629–34.

    Article  PubMed  CAS  Google Scholar 

  2. Sancar A. DNA repair in humans. Annu Rev Genet. 1995;29:69–105.

    Article  PubMed  CAS  Google Scholar 

  3. Wei Q, Matanoski GM, Farmer ER, Hedayati MA, Grossman L. DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. Proc Natl Acad Sci USA. 1993;90:1614–8.

    Article  PubMed  CAS  Google Scholar 

  4. Liu R, Yin LH, Pu YP. Reduced expression of human DNA repair genes in esophageal squamous-cell carcinoma in china. J Toxicol Environ Health A. 2007;70:956–63.

    Article  PubMed  CAS  Google Scholar 

  5. Sturgis EM, Zheng R, Li L, Castillo EJ, Eicher SA, Chen MH, et al. XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis. 2000;21:2219–23.

    Article  PubMed  CAS  Google Scholar 

  6. Sturgis EM, Castillo EJ, Li L, Zheng R, Eicher SA, Clayman GL, et al. Polymorphisms of DNA repair gene xrcc1 in squamous cell carcinoma of the head and neck. Carcinogenesis. 1999;20:2125–9.

    Article  PubMed  CAS  Google Scholar 

  7. Vodicka P, Stetina R, Polakova V, Tulupova E, Naccarati A, Vodickova L, et al. Association of DNA repair polymorphisms with DNA repair functional outcomes in healthy human subjects. Carcinogenesis. 2007;28:657–64.

    Article  PubMed  CAS  Google Scholar 

  8. Jaruga P, Zastawny TH, Skokowski J, Dizdaroglu M, Olinski R. Oxidative DNA base damage and antioxidant enzyme activities in human lung cancer. FEBS Lett. 1994;341:59–64.

    Article  PubMed  CAS  Google Scholar 

  9. Okamoto K, Toyokuni S, Uchida K, Ogawa O, Takenewa J, Kakehi Y, et al. Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. Int J Cancer. 1994;58:825–9.

    Article  PubMed  CAS  Google Scholar 

  10. Kondo S, Toyokuni S, Iwasa Y, Tanaka T, Onodera H, Hiai H, et al. Persistent oxidative stress in human colorectal carcinoma, but not in adenoma. Free Radic Biol Med. 1999;27:401–10.

    Article  PubMed  CAS  Google Scholar 

  11. Oliva MR, Ripoll F, Muñiz P, Iradi A, Trullenque R, Valls V, et al. Genetic alterations and oxidative metabolism in sporadic colorectal tumors from a Spanish community. Mol Carcinog. 1997;18:232–43.

    Article  PubMed  CAS  Google Scholar 

  12. Shibutani S, Takeshita M, Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodg. Nature. 1991;349:431–4.

    Article  PubMed  CAS  Google Scholar 

  13. Campalans A, Marsin S, Nakabeppu Y, O'connor TR, Boiteux S, Radicella JP. XRCC1 interactions with multiple DNA glycosylases: a model for its recruitment to base excision repair. DNA Repair (Amst). 2005;4:826–35.

    Article  CAS  Google Scholar 

  14. Lainé JP, Mocquet V, Bonfanti M, Braun C, Egly JM, Brousset P. Common XPD (ERCC2) polymorphisms have no measurable effect on nucleotide excision repair and basal transcription. DNA Repair (Amst). 2007;6:1264–70.

    Article  Google Scholar 

  15. Wood RD. DNA damage recognition during nucleotide excision repair in mammalian cells. Biochimie. 1999;81:39–44.

    Article  PubMed  CAS  Google Scholar 

  16. Lindahl T, Wood RD. Quality control by DNA repair. Science. 1999;286:1897–905.

    Article  PubMed  CAS  Google Scholar 

  17. Cheng L, Sturgis EM, Eicher SA, Spitz MR, Wei Q. Expression of nucleotide excision repair genes and the risk for squamous cell carcinoma of the head and neck. Cancer. 2002;94:393–7.

    Article  PubMed  CAS  Google Scholar 

  18. Morimoto H, Tsukada J, Kominato Y, Tanaka Y. Reduced expression of human mismatch repair genes in adult T-cell leukemia. Am J Hematol. 2005;78:100–7.

    Article  PubMed  CAS  Google Scholar 

  19. Wei QY, Eicher SA, Guan YL, Cheng L, Xu JL, Young LN, et al. Reduced expression of hMLH1 and hGTBPH/hMSH6: a risk factor for head and neck cancer. Cancer Epidemiol Biomarkers Prev. 1998;7:309–14.

    PubMed  CAS  Google Scholar 

  20. Anil K, Mohan PC, Hirdaya S, Shashi K. Associated risk of XRCC1 and XPD cross talk and life style factors in progression of head and neck cancer in north indian population. Mut Res-Fund Mol Mech Mutagen. 2011. doi:10.1016/j.mrfmmm.2011.09.001.

  21. Anil K, Mohan PC, Hirdaya S, Shashi K. Role of OGG1 Ser326Cys polymorphism and 8-oxoguanine dna damage in risk assessment of squamous cell carcinoma of head and neck in north indian population. Mutat Res-Gen Toxicol and Environ Mutagen. 2011. doi:10.1016/j.mrgentox.2011.09.015.

  22. Tarng DC, Liu TY, Huang TP. Protective effect of vitamin C on 8-hydroxy-2′-deoxyguanosine level in peripheral blood lymphocytes of chronic hemodialysis patients. Kidney Int. 2004;66:820–31.

    Article  PubMed  CAS  Google Scholar 

  23. Gao P, He P, Wang A, Xia T, Xu B, Xu Z, et al. Influence of pcb153 on oxidative DNA damage and DNA repair-related gene expression induced by pbde-47 in human neuroblastoma cells in vitro. Toxicol Sci. 2009;107:165–70.

    Article  PubMed  CAS  Google Scholar 

  24. Risom L, Dybdahl M, Bornholdt J, Vogel U, Wallin H, Moller P, et al. Oxidative DNA damage and defence gene expression in the mouse lung after short-term exposure to diesel exhaust particles by inhalation. Carcinogenesis. 2003;24:1847–52.

    Article  PubMed  CAS  Google Scholar 

  25. Genetic landscape of the people of india. A canvas for disease gene exploration. J Genet. 2008;87:3–20.

    Article  Google Scholar 

  26. Cheng L, Guan Y, Li L, Legerski RJ, Einspahr J, Bangert J, et al. Expression in normal human tissues of five nucleotide excision repair genes measured simultaneously by multiplex reverse transcription-polymerase chain reaction. Cancer Epidemiol Biomarkers Prev. 1999;8:801–7.

    PubMed  CAS  Google Scholar 

  27. Mayer C, Popanda O, Zelezny O, von Brevern MC, Bach A, Bartsch H, et al. DNA repair capacity after gamma-irradiation and expression profiles of dna repair genes in resting and proliferating human peripheral blood lymphocytes. DNA Repair (Amst). 2002;1:237–50.

    Article  CAS  Google Scholar 

  28. Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16:3219–25.

    Article  PubMed  CAS  Google Scholar 

  29. Takahashi Y, Moriwaki S, Sugiyama Y, Endo Y, Yamazaki K, Mori T, et al. Decreased gene expression responsible for post-ultraviolet DNA repair synthesis in aging: A possible mechanism of age-related reduction in DNA repair capacity. J Invest Dermatol. 2005;124:435–42.

    Article  PubMed  CAS  Google Scholar 

  30. Chen SK, Hsieh WA, Tsai MH, Chen CC, Hong AI, Wei YH, et al. Age-associated decrease of oxidative repair enzymes, human 8-oxoguanine dna glycosylases (hOGG1), in human aging. J Radiat Res. 2003;44:31–5.

    Article  PubMed  CAS  Google Scholar 

  31. Radak Z, Bori Z, Koltai E, Fatouros IG, Jamurtas AZ, Douroudos II, et al. Age-dependent changes in 8-oxoguanine DNA glycosylase activity are modulated by adaptive responses to physical exercise in human skeletal muscle. Free Radic Biol Med. 2011.

  32. Andrew AS, Karagas MR, Hamilton JW. Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. Int J Cancer. 2003;104:263–8.

    Article  PubMed  CAS  Google Scholar 

  33. Janssen K, Schlink K, Gotte W, Hippler B, Kaina B, Oesch F. DNA repair activity of 8-oxoguanine dna glycosylase 1 (ogg1) in human lymphocytes is not dependent on genetic polymorphism Ser(326)/Cys(326). Mutat Res-DNA Repair. 2001;486:207–16.

    Article  PubMed  CAS  Google Scholar 

  34. Chiba I, Takahashi T, Nau MM, D'Amico D, Curiel DT, Mitsudomi T, et al. Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung cancer study group. Oncogene. 1990;5:1603–10.

    PubMed  CAS  Google Scholar 

  35. Suzuki H, Takahashi T, Kuroishi T, Suyama M, Ariyoshi Y, Ueda R. P53 mutations in non-small cell lung cancer in japan: association between mutations and smoking. Cancer Res. 1992;52:734–6.

    PubMed  CAS  Google Scholar 

  36. Cheng L, Eicher SA, Guo ZZ, Hong WK, Spitz MR, Wei QY. Reduced DNA repair capacity in head and neck cancer patients. Cancer Epidemiol Biomarkers Prev. 1998;7:465–8.

    PubMed  CAS  Google Scholar 

  37. Caporaso N. The molecular epidemiology of oxidative damage to DNA and cancer. J Natl Cancer Inst. 2003;95:1263–5.

    PubMed  CAS  Google Scholar 

  38. Paz-Elizur T, Krupsky M, Elinger D, Schechtman E, Livneh Z. Repair of the oxidative DNA damage 8-oxoguanine as a biomarker for lung cancer risk. Cancer Biomark. 2005;1:201–5.

    PubMed  CAS  Google Scholar 

  39. Paz-Elizur T, Ben-Yosef R, Elinger D, Vexler A, Krupsky M, Berrebi A, et al. Reduced repair of the oxidative 8-oxoguanine DNA damage and risk of head and neck cancer. Cancer Res. 2006;66:11683–9.

    Article  PubMed  CAS  Google Scholar 

  40. Betti M, Ferrante D, Padoan M, Guarrera S, Giordano M, Aspesi A, et al. XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study. Mutat Res. 2011.

  41. Kowalski M, Przybylowska K, Rusin P, Olszewski J, Morawiec-Sztandera A, Bielecka-Kowalska A, et al. Genetic polymorphisms in DNA base excision repair gene XRCC1 and the risk of squamous cell carcinoma of the head and neck. J Exp Clin Cancer Res. 2009;28:37.

    Article  PubMed  Google Scholar 

  42. Chang JS, Wrensch MR, Hansen HM, Sison JD, Aldrich MC, Quesenberry CP, et al. Base excision repair genes and risk of lung cancer among san francisco bay area latinos and african-americans. Carcinogenesis. 2009;30:78–87.

    Article  PubMed  CAS  Google Scholar 

  43. Rodriguez M, Yu X, Chen J, Songyang Z. Phosphopeptide binding specificities of BRCA1 cooh-terminal (BRCT) domains. J Biol Chem. 2003;278:52914–8.

    Article  PubMed  CAS  Google Scholar 

  44. Radak Z, Boldogh I. 8-oxo-7,8-dihydroguanine: Links to gene expression, aging, and defense against oxidative stress. Free Radic Biol Med. 2010;49:587–96.

    Article  PubMed  CAS  Google Scholar 

  45. Thomas D, Scot AD, Barbey R, Padula M, Boiteux S. Inactivation of OGG1 increases the incidence of g. C–>t. A transversions in Saccharomyces cerevisiae: evidence for endogenous oxidative damage to DNA in eukaryotic cells. Mol Gen Genet. 1997;254:171–8.

    Article  PubMed  CAS  Google Scholar 

  46. Grollman AP, Moriya M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 1993;9:246–9.

    Article  PubMed  CAS  Google Scholar 

  47. Pylväs M, Puistola U, Laatio L, Kauppila S, Karihtala P. Elevated serum 8-OHdG is associated with poor prognosis in epithelial ovarian cancer. Anticancer Res. 2011;31:1411–5.

    PubMed  Google Scholar 

  48. Cheng L, Spitz MR, Hong WK, Wei Q. Reduced expression levels of nucleotide excision repair genes in lung cancer: a case-control analysis. Carcinogenesis. 2000;21:1527–30.

    Article  PubMed  CAS  Google Scholar 

  49. Vogel U, Nexø BA, Tjønneland A, Wallin H, Hertel O, Raaschou-Nielsen O. ERCC1, XPD and RAI mRNA levels in lymphocytes are not associated with lung cancer risk in a prospective study of danes. Mutat Res. 2006;593:88–96.

    PubMed  CAS  Google Scholar 

  50. Wei YC, Zhou FL, He DL, Bai JR, Hui LY, Wang XY, Nan KJ. The level of oxidative stress and the expression of genes involved in dna-damage signaling pathways in depressive patients with colorectal carcinoma. J Psychosom Res. 2009;66:259–266.

    Google Scholar 

  51. Habib SL. Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients. Mol Cancer. 2009;8:13.

    Article  PubMed  Google Scholar 

  52. Hatt L, Loft S, Risom L, Moller P, Sorensen M, Raaschou-Nielsen O, et al. OGG1 expression and OGG1 Ser326Cys polymorphism and risk of lung cancer in a prospective study. Mutat Res-Fund Mol Mech Mutagen. 2008;639:45–54.

    Article  CAS  Google Scholar 

  53. Polosak J, Roszkowska-Gancarz M, Kurylowicz A, Owczarz M, Dobosz P, Mossakowska M, et al. Decreased expression and the Lys751Gln polymorphism of the XPD gene are associated with extreme longevity. Biogerontology. 2010;11:287–97.

    Article  PubMed  CAS  Google Scholar 

  54. Deslee G, Adair-Kirk TL, Betsuyaku T, Woods JC, Moore CH, Gierada DS, et al. Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts. Am J Respir Cell Mol Biol. 2010;43:576–84.

    Article  PubMed  CAS  Google Scholar 

  55. Duell EJ, Wiencke JK, Cheng TJ, Varkonyi A, Zuo ZF, Ashok TDS, et al. Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis. 2000;21:965–71.

    Article  PubMed  CAS  Google Scholar 

  56. Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, et al. Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001;61:1354–7.

    PubMed  CAS  Google Scholar 

  57. Qiao Y, Spitz MR, Guo Z, Hadeyati M, Grossman L, Kraemer KH, et al. Rapid assessment of repair of ultraviolet dna damage with a modified host-cell reactivation assay using a luciferase reporter gene and correlation with polymorphisms of DNA repair genes in normal human lymphocytes. Mutat Res. 2002;509:165–74.

    PubMed  CAS  Google Scholar 

  58. Sliwinski T, Przybylowska K, Markiewicz L, Rusin P, Pietruszewska W, Zelinska-Blizniewska H, et al. MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study. Mol Biol Rep. 2010;38(2):1251–61.

    Article  PubMed  Google Scholar 

  59. Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S, Garte S, et al. DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006;27:997–1007.

    Article  PubMed  CAS  Google Scholar 

  60. Pastorelli R, Cerri A, Mezzetti M, Consonni E, Airoldi L. Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes. Int J Cancer. 2002;100:9–13.

    Article  PubMed  CAS  Google Scholar 

  61. Synowiec E, Stefanska J, Morawiec Z, Blasiak J, Wozniak K. Association between DNA damage, DNA repair genes variability and clinical characteristics in breast cancer patients. Mut Res-Fund Mol Mech Mutagenesis. 2008;648:65–72.

    Article  CAS  Google Scholar 

  62. Le Morvan V, Bellott R, Moisan F, Mathoulin-Pélissier S, Bonnet J, Robert J. Relationships between genetic polymorphisms and anticancer drug cytotoxicity vis-à-vis the nci-60 panel. Pharmacogenomics. 2006;7:843–52.

    Article  PubMed  Google Scholar 

  63. Rusin P, Olszewski J, Morawiec-Bajda A, Przybylowska K, Kaczmarczyk D, Golinska A, et al. Role of impaired DNA repair in genotoxic susceptibility of patients with head and neck cancer. Cell Biol Toxicol. 2009;25:489–97.

    Article  PubMed  CAS  Google Scholar 

  64. Rusin P, Olszewski J, Morawiec-Bajda A, Przybylowska K, Kaczmarczyk D, Golinska A, et al. Comparative study of DNA damage and repair in head and neck cancer after radiation treatment. Cell Biol Int. 2009;33:357–63.

    Article  PubMed  CAS  Google Scholar 

  65. Lai JI, Tzeng CH, Chen PM, Lin JK, Lin TC, Chen WS, et al. Very low prevalence of XPD K751Q polymorphism and its association with XPD expression and outcomes of FOLFOX-4 treatment in Asian patients with colorectal carcinoma. Cancer Sci. 2009;100:1261–6.

    Article  PubMed  CAS  Google Scholar 

  66. Wolfe KJ, Wickliffe JK, Hill CE, Paolini M, Ammenheuser MM, Abdel-Rahman SZ. Single nucleotide polymorphisms of the DNA repair gene XPD/ERCC2 alter mRNA expression. Pharmacogenet Genomics. 2007;17:897–905.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors are grateful to the Director of Indian Institute of Toxicology Research, Lucknow for his keen interest and support in carrying out the study. AK is thankful to UGC, New Delhi for providing Senior Research Fellowship. Financial support from CSIR Network Project SIP-08 is acknowledged; CSIR-IITR communication number 2954.

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Authors and Affiliations

  1. CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box 80, M.G. Marg, Lucknow, 226001, India

    Anil Kumar & Shashi Khandelwal

  2. C. S.M. Medical University, Lucknow, India

    Mohan Chand Pant

  3. Ch. Charan Singh University, Meerut, India

    Hirdya Shanker Singh

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  1. Anil Kumar
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Kumar, A., Pant, M.C., Singh, H.S. et al. Reduced expression of DNA repair genes (XRCC1, XPD, and OGG1) in squamous cell carcinoma of head and neck in North India. Tumor Biol. 33, 111–119 (2012). https://doi.org/10.1007/s13277-011-0253-7

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