Molecular Biology Reports

, Volume 38, Issue 2, pp 1251–1261 | Cite as

MUTYH Tyr165Cys, OGG1 Ser326Cys and XPD Lys751Gln polymorphisms and head neck cancer susceptibility: a case control study

  • Tomasz Sliwinski
  • Karolina Przybylowska
  • Lukasz Markiewicz
  • Pawel Rusin
  • Wioletta Pietruszewska
  • Hanna Zelinska-Blizniewska
  • Jurek Olszewski
  • Alina Morawiec-Sztandera
  • Wojciech Mlynarski
  • Ireneusz Majsterek


In the present study we investigated the association between three polymorphisms of the MUTYH (Tyr165Cys, rs34612342), the OGG1 (Ser326Cys, rs1052133) and the XPD (Lys751Gln, rs13181) genes with head and neck cancer risk. Genotypes were determined in DNA from peripheral blood lymphocytes of 265 patients with head and neck squamous cell carcinoma (HNSCC) as well as 280 cancer-free controls by PCR-restriction fragment lenght polymorphisms. We found an association between HNSCC and the Ser326Cys (OR 1.69; 95% CI 1.19–2.45) as well as Cys326Cys (OR 4.56; 95% CI 2.07–10.05) variants of the OGG1 gene. The gene–gene interaction between MUTYH and OGG1 as well as OGG1 and XPD polymorphic variants may contribute to higher prevalence of HNSCC. We also found an association between Ser326Cys and Cys326Cys variants of OGG1 gene and smoking status in HNSCC patients (OR 1.97; 95% CI 1.25–3.11), (OR 3.54; 95% CI 1.39–9.04), respectively. Moreover, we also observed a protective association between Tyr165Cys variant of the MUTYH gene and non-smoking status in HNSCC (OR 0.34; 95% CI 0.17–0.66). We also found a link between gene–gene interaction (MUTYH and OGG1 or OGG1 and XPD) and smoking (ORs 2.17–4.20 and 2.18–5.23) or non-smoking status (ORs 0.11 and 7.61) in HNSCC patients, respectively. In conclusion our data showed that the Ser326Cys polymorphism of the OGG1 gene may modify the risk of HNSCC associated with smoking. Finally we suggested that this polymorphism might be used as predictive factor for head and neck cancer in Polish population.


MUTYH OGG1 XPD Gene polymorphism Head and neck cancer 



This work was supported by Grant N301 099 32/3581 from Polish Ministry of Science and Higher Education.

Conflict of interests

The authors declare that there are no conflicts of interests.


  1. 1.
    Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ (2004) American Cancer Society. Cancer statistics. CA Cancer J Clin 54:8–29CrossRefPubMedGoogle Scholar
  2. 2.
    Parkin DM, Pisani P, Ferlay J (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int J Cancer 54:594–606CrossRefPubMedGoogle Scholar
  3. 3.
    Gupta PC, Murti PR, Bhonsle RB (1996) Epidemiology of cancer by tobacco products and its significance of TSNA. Crit Rev Toxicol 26:83–98CrossRefGoogle Scholar
  4. 4.
    Morawiec-Sztandera A, Zimmer-Nowicka J, Kaczmarczyk D, Niedźwiecka I (2008) Use of tissue autofluorescence in the diagnostics and assessment of treatment efficacy of the head and neck cancer. Otolaryngol Pol 62:540–544PubMedGoogle Scholar
  5. 5.
    Crowe DL (2002) Molecular pathology of head and neck cancer. Histol Histopathol 17:909–914PubMedGoogle Scholar
  6. 6.
    Vassallo R, Kroening PR, Parambil J, Kita H (2008) Nicotine and oxidative cigarette smoke constituents induce immune-modulatory and pro-inflammatory dendritic cell responses. Mol Immunol 45:3321–3329CrossRefPubMedGoogle Scholar
  7. 7.
    Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40CrossRefPubMedGoogle Scholar
  8. 8.
    Hoeijmakers JH (1993) Nucleotide excision repair. II: From yeast to mammals. Trends Genet 9:211–217CrossRefPubMedGoogle Scholar
  9. 9.
    Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L, Kayser K, Dienemann H, Schulz V, Drings P, Bartsch H, Schmezer P (2004) Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis 25:2433–2441CrossRefPubMedGoogle Scholar
  10. 10.
    Yu Z, Chen J, Ford BN, Brackley ME, Glickman BW (1999) Human DNA repair systems: an overview. Environ Mol Mutagen 33:3–20CrossRefPubMedGoogle Scholar
  11. 11.
    Wood RD, Mitchell M, Sgouros J, Lindahl T (2001) Human DNA repair genes. Science 291:1284–1289CrossRefPubMedGoogle Scholar
  12. 12.
    Kowalski M, Przybylowska K, Rusin P, Olszewski J, Morawiec-Sztandera A, Bielecka-Kowalska A, Pietruszewska W, Mlynarski W, Janusz S, Majsterek I (2009) 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 13:28–37Google Scholar
  13. 13.
    Tse D, Zhai R, Zhou W, Heist RS, Asomaning K, Su L, Lynch TJ, Wain JC, Christiani DC, Liu G (2008) Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer Causes Control 19:1077–1083CrossRefPubMedGoogle Scholar
  14. 14.
    Liu G, Zhou W, Yeap BY, Su L, Wain JC, Poneros JM, Nishioka NS, Lynch TJ, Christiani DC (2007) XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis 28:1254–1258CrossRefPubMedGoogle Scholar
  15. 15.
    Lee YC, Morgenstern H, Greenland S, Tashkin DP, Papp J, Sinsheimer J, Cao W, Hashibe M, You NC, Mao JT, Cozen W, Mack TM, Zhang ZF (2008) A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancers. Int J Cancer 122:1630–1638CrossRefPubMedGoogle Scholar
  16. 16.
    Marra G, Jiricny J (2003) Multiple colorectal adenomas–Is their number up? N Engl J Med 348:845–847CrossRefPubMedGoogle Scholar
  17. 17.
    Elahi A, Zheng Z, Park J, Eyring K, McCaffrey T, Lazarus P (2002) The human OGG1 DNA repair enzyme and its association with orolaryngeal cancer risk. Carcinogenesis 23:1229–1234CrossRefPubMedGoogle Scholar
  18. 18.
    Dherin C, Radicella JP, Dizdaroglu M, Boiteux S (1999) Excision of oxidatively damaged DNA bases by the human alpha-hOgg1 protein and the polymorphic alpha-hOgg1 (Ser326Cys) protein which is frequently found in human populations. Nucleic Acids Res 27:4001–4007CrossRefPubMedGoogle Scholar
  19. 19.
    Nakabeppu Y, Tsuchimoto D, Furuichi M, Sakumi K (2004) The defense mechanisms in mammalian cells against oxidative damage in nucleic acids and their involvement in the suppression of mutagenesis and cell death. Free Radic Res 38:423–429CrossRefPubMedGoogle Scholar
  20. 20.
    Tao H, Shinmura K, Suzuki M, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N, Sugimura H (2008) Association between genetic polymorphisms of the base excision repair gene MUTYH and increased colorectal cancer risk in a Japanese population. Cancer Sci 99:355–360CrossRefPubMedGoogle Scholar
  21. 21.
    Lehmann AR (2001) The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes Dev 15:15–23CrossRefPubMedGoogle Scholar
  22. 22.
    Hemminki K, Xu G, Angelini S, Snellman E, Jansen CT, Lambert B, Hou SM (2001) XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 22:1185–1188CrossRefPubMedGoogle Scholar
  23. 23.
    Au WW, Salama SA, Sierra-Torres CH (2003) Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect 111:1843–1850CrossRefPubMedGoogle Scholar
  24. 24.
    Lunn RM, Helzlsouer KJ, Parshad R, Umbach DM, Harris EL, Sanford KK, Bell DA (2000) XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 21:551–555CrossRefPubMedGoogle Scholar
  25. 25.
    Stern MC, Siegmund KD, Conti DV, Corral R, Haile RW (2006) XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 15:2384–2390CrossRefPubMedGoogle Scholar
  26. 26.
    Hansen RD, Sørensen M, Tjønneland A, Overvad K, Wallin H, Raaschou-Nielsen O, Vogel U (2007) XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer. Mutat Res 619:68–80PubMedGoogle Scholar
  27. 27.
    Buch S, Zhu B, Davis AG, Odom D, Siegfried JM, Grandis JR, Romkes M (2005) Association of polymorphisms in the cyclin D1 and PD genes and susceptibility to cancers of the upper aero-digestive tract. Mol Carcinog 42:222–228CrossRefPubMedGoogle Scholar
  28. 28.
    Piccioli P, Serra M, Gismondi V, Pedemonte S, Loiacono F, Lastraioli S, Bertario L, De Angioletti M, Varesco L, Notaro R (2006) Multiplex tetra-primer amplification refractory mutation system PCR to detect 6 common germline mutations of the MUTYH gene associated with polyposis and colorectal cancer. Clin Chem 52:739–743CrossRefPubMedGoogle Scholar
  29. 29.
    Barnes DE, Lindahl T (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 38:445–476CrossRefPubMedGoogle Scholar
  30. 30.
    Krokan HE, Nilsen H, Skorpen F, Otterlei M, Slupphaug G (2000) Base excision repair of DNA in mammalian cells. FEBS Lett 476:73–77CrossRefPubMedGoogle Scholar
  31. 31.
    Nohmi T, Kim SR, Yamada M (2005) Modulation of oxidative mutagenesis and carcinogenesis by polymorphic forms of human DNA repair enzymes. Mutat Res 591:60–73PubMedGoogle Scholar
  32. 32.
    Arcand SL, Provencher D, Mes-Masson AM, Tonin PN (2005) OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer. Int J Oncol 27:1315–1320PubMedGoogle Scholar
  33. 33.
    Sugimura H, Kohno T, Wakai K, Nagura K, Genka K, Igarashi H, Morris BJ, Baba S, Ohno Y, Gao C, Li Z, Wang J, Takezaki T, Tajima K, Varga T, Sawaguchi T, Lum JK, Martinson JJ, Tsugane S, Iwamasa T, Shinmura K, Yokota J (1999) hOGG1 Ser326Cys polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 8:669–674PubMedGoogle Scholar
  34. 34.
    Xing DY, Tan W, Song N, Lin DX (2001) Ser326Cys polymorphism in hOGG1 gene and risk of esophageal cancer in a Chinese population. Int J Cancer 95:140–143CrossRefPubMedGoogle Scholar
  35. 35.
    Xu J, Zheng SL, Turner A, Isaacs SD, Wiley KE, Hawkins GA, Chang BL, Bleecker ER, Walsh PC, Meyers DA, Isaacs WB (2002) Associations between hOGG1 sequence variants and prostate cancer susceptibility. Cancer Res 62:2253–2257PubMedGoogle Scholar
  36. 36.
    Monteiro E, Varzim G, Silva R, da Costa B, Lopes C (2005) Polymorphisms of the human OGG1 gene in laryngeal cancer: implications in radiotherapy response and survival. Rev Laryngol Otol Rhinol (Bord) 126:135–140Google Scholar
  37. 37.
    Takezaki T, Gao CM, Wu JZ, Li ZY, Wang JD, Ding JH, Liu YT, Hu X, Xu TL, Tajima K, Sugimura H (2002) hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. Int J Cancer 99:624–627CrossRefPubMedGoogle Scholar
  38. 38.
    Tsukino H, Hanaoka T, Otani T, Iwasaki M, Kobayashi M, Hara M, Natsukawa S, Shaura K, Koizumi Y, Kasuga Y, Tsugane S (2004) hOGG1 Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations. Cancer Sci 95:977–983CrossRefPubMedGoogle Scholar
  39. 39.
    Vogel U, Olsen A, Wallin H, Overvad K, Tjønneland A, Nexø BA (2004) No association between OGG1 Ser326Cys and risk of basal cell carcinoma. Cancer Epidemiol Biomarkers Prev 13:1680–1681PubMedGoogle Scholar
  40. 40.
    Hashimoto T, Uchida K, Okayama N, Imate Y, Suehiro Y, Hamanaka Y, Ueyama Y, Yamashita H, Hinoda Y (2005) Interaction of OGG1 Ser326Cys polymorphism with cigarette smoking in head and neck squamous cell carcinoma. Mol Carcinog 45:344–348CrossRefGoogle Scholar
  41. 41.
    Pawlowska E, Janik-Papis K, Rydzanicz M, Zuk K, Kaczmarczyk D, Olszewski J, Szyfter K, Blasiak J, Morawiec-Sztandera A (2009) The Cys326 allele of the 8-oxoguanine DNA N-glycosylase 1 gene as a risk factor in smoking- and drinking-associated larynx cancer. Tohoku J Exp Med 219:269–275CrossRefPubMedGoogle Scholar
  42. 42.
    Stanczyk M, Sliwinski T, Cuchra M, Zubowska M, Bielecka-Kowalska A, Kowalski M, Szemraj J, Mlynarski W, Majsterek I (2010) The association of polymorphisms in DNA base excision repair genes XRCC1, OGG1 and MUTYH with the risk of childhood acute lymphoblastic leukemia. Mol Biol Rep. doi: 10.1007/s11033-010-0127-x
  43. 43.
    Sliwinski T, Markiewicz L, Rusin P, Pietruszewska W, Olszewski J, Morawiec-Sztandera A, Mlynarski W, Majsterek I (2009) Polymorphisms of the DNA base excision repair gene MUTYH in head and neck cancer. Exp Oncol 31:57–59PubMedGoogle Scholar
  44. 44.
    Görgens H, Müller A, Krüger S, Kuhlisch E, König IR, Ziegler A, Schackert HK, Eckelt U (2007) Analysis of the base excision repair genes MTH1, OGG1 and MUTYH in patients with squamous oral carcinomas. Oral Oncol 43:791–795CrossRefPubMedGoogle Scholar
  45. 45.
    Li C, Hu Z, Liu Z, Wang LE, Strom SS, Gershenwald JE, Lee JE, Ross MI, Mansfield PF, Cormier JN, Prieto VG, Duvic M, Grimm EA, Wei Q (2006) Polymorphisms in the DNA repair genes XPC, XPD, and XPG and risk of cutaneous melanoma: a case-control analysis. Cancer Epidemiol Biomarkers Prev 15:2526–2532CrossRefPubMedGoogle Scholar
  46. 46.
    Lunn RM, Langlois RG, Hsieh LL, Thompson CL, Bell DA (1999) XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequency. Cancer Res 59:2557–2561PubMedGoogle Scholar
  47. 47.
    Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, Guo Z, Lei L, Mohrenweiser H, Wei Q (2001) Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res 61:1354–1357PubMedGoogle Scholar
  48. 48.
    Benhamou S, Sarasin A (2002) ERCC2/XPD gene polymorphisms and cancer risk. Mutagenesis 17:463–469CrossRefPubMedGoogle Scholar
  49. 49.
    Xing D, Qi J, Miao X, Lu W, Tan W, Lin D (2002) Polymorphisms of DNA repair genes XRCC1 and XPD and their associations with risk of esophageal squamous cell carcinoma in a Chinese population. Int J Cancer 100:600–605CrossRefPubMedGoogle Scholar
  50. 50.
    Shi Q, Wang LE, Bondy ML, Brewster A, Singletary SE, Wei Q (2004) Reduced DNA repair of benzo[a]pyrene diol epoxideinduced adducts and common XPD polymorphisms in breast cancer patients. Carcinogenesis 25:1695–1700CrossRefPubMedGoogle Scholar
  51. 51.
    Hu JJ, Hall MC, Grossman L, Hedayati M, McCullough DL, Lohman K, Case LD (2004) Deficient nucleotide excision repair capacity enhances human prostate cancer risk. Cancer Res 64:1197–1201CrossRefPubMedGoogle Scholar
  52. 52.
    Benhamou S, Sarasin A (2005) ERCC2/XPD gene polymorphisms and lung cancer: a HuGE review. Am J Epidemiol 161:1–14CrossRefPubMedGoogle Scholar
  53. 53.
    Hill JW, Evans MK (2006) Dimerization and opposite base-dependent catalytic impairment of polymorphic S326C OGG1 glycosylase. Nucleic Acids Res 34:1620–1632CrossRefPubMedGoogle Scholar
  54. 54.
    Ye W, Kumar R, Bacova G, Lagergren J, Hemminki K, Nyren O (2006) The XPD 751Gln allele is associated with an increased risk for esophageal adenocarcinoma: a population-based case-control study in Sweden. Carcinogenesis 27:1835–1841CrossRefPubMedGoogle Scholar
  55. 55.
    Casson AG, Zheng Z, Evans SC, Veugelers PJ, Porter GA, Guernsey DL (2005) Polymorphisms in DNA repair genes in the molecular pathogenesis of esophageal (Barrett) adenocarcinoma. Carcinogenesis 26:1536–1541CrossRefPubMedGoogle Scholar
  56. 56.
    Ferguson HR, Wild CP, Anderson LA, Murphy SJ, Johnston BT, Murray LJ, Watson RG, McGuigan J, Reynolds JV, Hardie LJ (2008) No association between hOGG1, XRCC1, and XPD polymorphisms and risk of reflux esophagitis, Barrett’s esophagus, or esophageal adenocarcinoma: results from the factors influencing the Barrett’s adenocarcinoma relationship case-control study. Cancer Epidemiol Biomarkers Prev 17:736–739CrossRefPubMedGoogle Scholar
  57. 57.
    Hashimoto T, Uchida K, Okayama N, Imate Y, Suehiro Y, Hamanaka Y, Ueyama Y, Yamashita H, Hinoda Y (2006) Interaction of OGG1 Ser326Cys polymorphism with cigarette smoking in head and neck squamous cell carcinoma. Mol Carcinog 45:344–348CrossRefPubMedGoogle Scholar
  58. 58.
    Bau DT, Tsai MH, Huang CY, Lee CC, Tseng HC, Lo YL, Tsai Y, Tsai FJ (2007) Relationship between polymorphisms of nucleotide excision repair genes and oral cancer risk in Taiwan: evidence for modification of smoking habit. Chin J Physiol 50:294–300PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Tomasz Sliwinski
    • 1
  • Karolina Przybylowska
    • 2
  • Lukasz Markiewicz
    • 2
  • Pawel Rusin
    • 1
  • Wioletta Pietruszewska
    • 3
  • Hanna Zelinska-Blizniewska
    • 4
  • Jurek Olszewski
    • 4
  • Alina Morawiec-Sztandera
    • 5
  • Wojciech Mlynarski
    • 6
  • Ireneusz Majsterek
    • 1
    • 2
  1. 1.Department of Molecular GeneticsUniversity of LodzLodzPoland
  2. 2.Department of Clinical Chemistry and BiochemistryMedical University of LodzLodzPoland
  3. 3.Department of OtolaryngologyMedical University of LodzLodzPoland
  4. 4.Department of Otolaryngology and OncologyMedical University of LodzLodzPoland
  5. 5.Department of Head and Neck CancerMedical University of LodzLodzPoland
  6. 6.Department of PediatricsMedical University of LodzLodzPoland

Personalised recommendations