Host and Viral Genetics and Risk of Cervical Cancer

  • Janet S. Rader
Part of the Cancer Genetics book series (CANGENETICS)


Cervical cancer is the third most common malignant disease in women, with an annual worldwide incidence of 493,243 cases. It is a leading cause of cancer death in developing countries [1]. Even in the United States, cervical cancer is still the number three cause of cancer death in women aged 15–34 and the number five cause in women aged 35–54 [2]. Therefore, the disease ranks fourth for average years of life lost from cancer, and it disproportionately affects minority groups and women of low socioeconomic status [2]Cervical cancer is the third most common malignant disease in women, with an annual worldwide incidence of 493,243 cases. It is a leading cause of cancer death in developing countries [1]. Even in the United States, cervical cancer is still the number three cause of cancer death in women aged 15–34 and the number five cause in women aged 35–54 [2]. Therefore


Cervical Cancer Invasive Cervical Cancer Severe Combine Immune Deficiency Cervical Squamous Cell Carcinoma Leukocyte Adhesion Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported, in part, by NIH grants CA95713 and CA94141.


  1. 1.
    Parkin DM, Bray F, Ferlay J, et al. (2005) Global cancer statistics, 2002. CA Cancer J Clin 55: 74–108.PubMedGoogle Scholar
  2. 2.
    NCHS. National Center for Health Statistics (NCHS) Public-use file for 1998 deaths.Google Scholar
  3. 3.
    Walboomers JM, Jacobs MV, Manos MM, et al. (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189: 12–19.PubMedGoogle Scholar
  4. 4.
    Gius D, Funk MC, Chuang EY, et al. (2007) Profiling microdissected epithelium and stroma to model genomic signatures for cervical carcinogenesis accommodating for covariates. Cancer Res 67: 7113–7123.PubMedGoogle Scholar
  5. 5.
    Collins Y, Einstein MH, Gostout BS, et al. (2006) Cervical cancer prevention in the era of prophylactic vaccines: a preview for gynecologic oncologists. Gynecol Oncol 102: 552–562.PubMedGoogle Scholar
  6. 6.
    Plummer M, Franceschi S (2002) Strategies for HPV prevention. Virus Res 89: 285–293.PubMedGoogle Scholar
  7. 7.
    Sawaya GF, Brown AD, Washington AE, et al. (2001) Current approaches to cervical-cancer screening. N Engl J Med 344: 1603–1607.PubMedGoogle Scholar
  8. 8.
    Appleby P, Beral V, Berrington de Gonzalez A, et al. (2007) Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet 370: 1609–1621.PubMedGoogle Scholar
  9. 9.
    Munoz N, Franceschi S, Bosetti C, et al. (2002) Role of parity and human papillomavirus in cervical cancer: the IARC multicentric case–control study. Lancet 359: 1093–1101.PubMedGoogle Scholar
  10. 10.
    Plummer M, Herrero R, Franceschi S, et al. (2003) Smoking and cervical cancer: pooled analysis of the IARC multi-centric case–control study. Cancer Causes Control 14: 805–814.PubMedGoogle Scholar
  11. 11.
    Shields TS, Brinton LA, Burk RD, et al. (2004) A case–control study of risk factors for invasive cervical cancer among U.S. women exposed to oncogenic types of human papillomavirus. Cancer Epidemiol Biomarkers Prev 13: 1574–1582.PubMedGoogle Scholar
  12. 12.
    Jensen SE, Lehman B, Antoni MH, et al. (2007) Virally mediated cervical cancer in the iatrogenically immunocompromised: applications for psychoneuroimmunology. Brain Behav Immun 21: 758–766.PubMedGoogle Scholar
  13. 13.
    Baseman JG, Koutsky LA (2005) The epidemiology of human papillomavirus infections. J Clin Virol 32: 16–24.Google Scholar
  14. 14.
    Castle PE, Schiffman M, Herrero R, et al. (2005) A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica. J Infect Dis 191: 1808–1816.PubMedGoogle Scholar
  15. 15.
    Khan MJ, Partridge EE, Wang SS, et al. (2005) Socioeconomic status and the risk of cervical intraepithelial neoplasia grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology. Cancer 104: 61–70.PubMedGoogle Scholar
  16. 16.
    Nasiell K, Roger V, Nasiell M (1986) Behavior of mild dysplasia during long-term follow-up. Obstet Gynecol 67: 665–669.PubMedGoogle Scholar
  17. 17.
    Östör AG (1993) Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol 12: 186–192.PubMedGoogle Scholar
  18. 18.
    Follen M, Vlastos AT, Meyskens FL, Jr., et al. (2002) Why phase II trials in cervical chemoprevention are negative: what have we learned? Cancer Causes Control 13: 855–873.PubMedGoogle Scholar
  19. 19.
    Hebner CM, Laimins LA (2006) Human papillomaviruses: basic mechanisms of pathogenesis and oncogenicity. Rev Med Virol 16: 83–97.PubMedGoogle Scholar
  20. 20.
    Nguyen DX, Westbrook TF, McCance DJ (2002) Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol 76: 619–632.PubMedGoogle Scholar
  21. 21.
    Werness BA, Levine AJ, Howley PM (1990) Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 248: 76–79.PubMedGoogle Scholar
  22. 22.
    Pett M, Coleman N (2007) Integration of high-risk human papillomavirus: a key event in cervical carcinogenesis? J Pathol 212: 356–367.PubMedGoogle Scholar
  23. 23.
    Bosch FX, Manos MM, Muñoz N, et al. (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 87: 796–802.PubMedGoogle Scholar
  24. 24.
    Castle PE, Solomon D, Schiffman M, et al. (2005) Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Natl Cancer Inst 97: 1066–1071.PubMedGoogle Scholar
  25. 25.
    Londesborough P, Ho L, Terry G, et al. (1996) Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities. Int J Cancer 69: 364–368.PubMedGoogle Scholar
  26. 26.
    Xi LF, Koutsky LA, Galloway DA, et al. (1997) Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia. J Natl Cancer Inst 89: 796–802.PubMedGoogle Scholar
  27. 27.
    Zehbe I, Voglino G, Delius H, et al. (1998) Risk of cervical cancer and geographical variations of human papillomavirus 16 E6 polymorphisms. Lancet 352: 1441–1442.PubMedGoogle Scholar
  28. 28.
    Muñoz N, Bosch FX, Sanjosé S, et al. (2003) Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 348: 518–527.PubMedGoogle Scholar
  29. 29.
    Ho GY, Burk RD, Klein S, et al. (1995) Persistent genital human papillomavirus infection as a risk factor for persistent cervical dysplasia. J Natl Cancer Inst 87: 1365–1371.PubMedGoogle Scholar
  30. 30.
    Remmink AJ, Walboomers JM, Helmerhorst TJ, et al. (1995) The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months. Int J Cancer 61: 306–311.PubMedGoogle Scholar
  31. 31.
    Romney SL, Ho GYF, Palan PR, et al. (1997) Effects of B-carotene and other factors on outcome of cervical dysplasia and human papillomavirus infection. Gynecol Oncol 65: 483–492.PubMedGoogle Scholar
  32. 32.
    Bernard HU, Calleja-Macias IE, Dunn ST (2006) Genome variation of human papillomavirus types: phylogenetic and medical implications. Int J Cancer 118: 1071–1076.PubMedGoogle Scholar
  33. 33.
    Calleja-Macias IE, Kalantari M, Huh J, et al. (2004) Genomic diversity of human papillomavirus-16, 18, 31, and 35 isolates in a Mexican population and relationship to European, African, and Native American variants. Virology 319: 315–323.PubMedGoogle Scholar
  34. 34.
    Chen Z, Terai M, Fu L, et al. (2005) Diversifying selection in human papillomavirus type 16 lineages based on complete genome analyses. J Virol 79: 7014–7023.PubMedGoogle Scholar
  35. 35.
    Ho L, Chan SY, Burk RD, et al. (1993) The genetic drift of human papillomavirus type 16 is a means of reconstructing prehistoric viral spread and the movement of ancient human populations. J Virol 67: 6413–6423.PubMedGoogle Scholar
  36. 36.
    Ong CK, Chan SY, Campo MS, et al. (1993) Evolution of human papillomavirus type 18: an ancient phylogenetic root in Africa and intratype diversity reflect coevolution with human ethnic groups. J Virol 67: 6424–6431.PubMedGoogle Scholar
  37. 37.
    Calleja-Macias IE, Villa LL, Prado JC, et al. (2005) Worldwide genomic diversity of the high-risk human papillomavirus types 31, 35, 52, and 58, four close relatives of human papillomavirus type 16. J Virol 79: 13630–13640.PubMedGoogle Scholar
  38. 38.
    Stoppler MC, Ching K, Stoppler H, et al. (1996) Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation. J Virol 70: 6987–6993.PubMedGoogle Scholar
  39. 39.
    Slebos RJC, Kessis TD, Chen AW, et al. (1995) Functional consequences of directed mutations in human papillomavirus E6 proteins: abrogation of p53-mediated cell cycle arrest correlates with p53 binding and degradation in vitro. Virology 208: 111–120.PubMedGoogle Scholar
  40. 40.
    May M, Dong XP, Beyer-Finkler E, et al. (1994) The E6/E7 promoter of extrachromosomal HPV16 DNA in cervical cancers escapes from cellular repression by mutation of target sequences for YY1. Embo J 13: 1460–1466.PubMedGoogle Scholar
  41. 41.
    Pastrana DV, Vass WC, Lowy DR, et al. (2001) NHPV16 VLP vaccine induces human antibodies that neutralize divergent variants of HPV16. Virology 279: 361–369.PubMedGoogle Scholar
  42. 42.
    Yang R, Wheeler CM, Chen X, et al. (2005) Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer. J Virol 79: 6741–6750.PubMedGoogle Scholar
  43. 43.
    Nindl I, Rindfleisch K, Lotz B, et al. (1999) Uniform distribution of HPV 16 E6 and E7 variants in patients with normal histology, cervical intra-epithelial neoplasia and cervical cancer. Int J Cancer 82: 203–207.PubMedGoogle Scholar
  44. 44.
    Yamada T, Manos MM, Peto J, et al. (1997) Human papillomavirus type 16 sequence variation in cervical cancers: a worldwide perspective. J Virol 71: 2463–2472.PubMedGoogle Scholar
  45. 45.
    Xi LF, Kiviat NB, Hildesheim A, et al. (2006) Human papillomavirus type 16 and 18 variants: race-related distribution and persistence. J Natl Cancer Inst 98: 1045–1052.PubMedGoogle Scholar
  46. 46.
    Ting AH, McGarvey KM, Baylin SB (2006) The cancer epigenome–components and functional correlates. Genes Dev 20: 3215–3231.PubMedGoogle Scholar
  47. 47.
    Rosl F, Arab A, Klevenz B, et al. (1993) The effect of DNA methylation on gene regulation of human papillomaviruses. J Gen Virol 74(Pt 5): 791–801.PubMedGoogle Scholar
  48. 48.
    Kalantari M, Lee D, Calleja-Macias IE, et al. (2008) Effects of cellular differentiation, chromosomal integration and 5-aza-2′-deoxycytidine treatment on human papillomavirus-16 DNA methylation in cultured cell lines. Virology 374: 292–303.PubMedGoogle Scholar
  49. 49.
    Van Tine BA, Kappes JC, Banerjee NS, et al. (2004) Clonal selection for transcriptionally active viral oncogenes during progression to cancer. J Virol 78: 11172–11186.PubMedGoogle Scholar
  50. 50.
    Badal S, Badal V, Calleja-Macias IE, et al. (2004) The human papillomavirus-18 genome is efficiently targeted by cellular DNA methylation. Virology 324: 483–492.PubMedGoogle Scholar
  51. 51.
    Turan T, Kalantari M, Calleja-Macias IE, et al. (2006) Methylation of the human papillomavirus-18 L1 gene: a biomarker of neoplastic progression? Virology 349: 175–183.PubMedGoogle Scholar
  52. 52.
    Badal V, Chuang LS, Tan EH, et al. (2003) CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens: genomic hypomethylation correlates with carcinogenic progression. J Virol 77: 6227–6234.PubMedGoogle Scholar
  53. 53.
    Kalantari M, Calleja-Macias IE, Tewari D, et al. (2004) Conserved methylation patterns of human papillomavirus type 16 DNA in asymptomatic infection and cervical neoplasia. J Virol 78: 12762–12772.PubMedGoogle Scholar
  54. 54.
    Bhattacharjee B, Sengupta S (2006) CpG methylation of HPV 16 LCR at E2 binding site proximal to P97 is associated with cervical cancer in presence of intact E2. Virology 354: 280–285.PubMedGoogle Scholar
  55. 55.
    Kim K, Garner-Hamrick PA, Fisher C, et al. (2003) Methylation patterns of papillomavirus DNA, its influence on E2 function, and implications in viral infection. J Virol 77: 12450–12459.PubMedGoogle Scholar
  56. 56.
    Magnusson PKE, Sparén P, Gyllensten UB (1999) Genetic link to cervical tumours. Nature 400: 29–30.PubMedGoogle Scholar
  57. 57.
    Magnusson PEK, Litchtenstein P, Gyllensten UB (2000) Heritability of cervical tumours. Int J Cancer 88: 698–701.PubMedGoogle Scholar
  58. 58.
    Hemminki K, Dong C, Vaittinen P (1999) Familial risks in cervical cancer: Is there a hereditary component? Int J Cancer 82: 775–781.PubMedGoogle Scholar
  59. 59.
    Hemminki K, Bermejo JL (2005) Relationships between familial risks of cancer and the effects of heritable genes and their SNP variants. Mutat Res 592: 6–17.PubMedGoogle Scholar
  60. 60.
    Ahlbom A, Lichtenstein P, Malmström H, et al. (1997) Cancer in twins: genetic and nongenetic familial risk factors. J Natl Cancer Inst 89: 287–293.PubMedGoogle Scholar
  61. 61.
    Furgyik S, Grubb R, Kullander S, et al. (1986) Familial occurrence of cervical cancer, stages 0–IV. Acta Obstet Gynecol Scand 65: 223–227.PubMedGoogle Scholar
  62. 62.
    Albert S (1977) Familial cancer in the general population. Cancer 40: 1674–1679.PubMedGoogle Scholar
  63. 63.
    Rotkin ID (1966) Further studies in cervical cancer inheritance. Cancer 19: 1251–1268.PubMedGoogle Scholar
  64. 64.
    Engelmark MT, Ivansson EL, Magnusson JJ, et al. (2006) Identification of susceptibility loci for cervical carcinoma by genome scan of affected sib-pairs. Hum Mol Genet 15: 3351–3360.PubMedGoogle Scholar
  65. 65.
    Orth G (2006) Genetics of epidermodysplasia verruciformis: Insights into host defense against papillomaviruses. Semin Immunol 18: 362–374.PubMedGoogle Scholar
  66. 66.
    Gaspar HB, Harwood C, Leigh I, et al. (2004) Severe cutaneous papillomavirus disease after haematopoietic stem-cell transplantation in patients with severe combined immunodeficiency. Br J Haematol 127: 232–233.PubMedGoogle Scholar
  67. 67.
    Laffort C, Le Deist F, Favre M, et al. (2004) Severe cutaneous papillomavirus disease after haemopoietic stem-cell transplantation in patients with severe combined immune deficiency caused by common gammac cytokine receptor subunit or JAK-3 deficiency. Lancet 363: 2051–2054.PubMedGoogle Scholar
  68. 68.
    Tindle RW (2002) Immune evasion in human papillomavirus-associated cervical cancer. Nat Rev Cancer 2: 59–65.PubMedGoogle Scholar
  69. 69.
    Hildesheim A, Wang SS (2002) Host and viral genetics and risk of cervical cancer: a review. Virus Res 89: 229–240.PubMedGoogle Scholar
  70. 70.
    Zoodsma M, Nolte IM, Te Meerman GJ, et al. (2005) HLA genes and other candidate genes involved in susceptibility for (pre)neoplastic cervical disease. Int J Oncol 26: 769–784.PubMedGoogle Scholar
  71. 71.
    Wank R, Thomssen C (1991) High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352: 723–725.PubMedGoogle Scholar
  72. 72.
    Wank R, Thomssen C (1992) HLA antigens and cervical carcinoma. Nature 356: 22–23.PubMedGoogle Scholar
  73. 73.
    Helland Å, BØrresen A-L, Kristensen G, et al. (1994) DQA1 and DQB1 genes in patients with squamous cell carcinoma of the cervix: relationship to human papillomavirus infection and prognosis. Cancer Epidemiol Biomarkers Prev 3: 479–486.PubMedGoogle Scholar
  74. 74.
    Nawa A, Nishiyama Y, Kobayashi T, et al. (1995) Association of human leukocyte antigen-B1*03 with cervical cancer in Japanese women aged 35 years and younger. Cancer 75: 518–521.PubMedGoogle Scholar
  75. 75.
    Mehal WZ, Lo Y-MD, Herrington CS, et al. (1994) Role of human papillomavirus in determining the HLA associated risk of cervical carcinogenesis. J Clin Pathol 47: 1077–1081.PubMedGoogle Scholar
  76. 76.
    Sastre-Garau X, Loste M-N, Vincent-Salomon A, et al. (1996) Decreased frequency of HLA-DRB1*13 alleles in Frenchwomen with HPV-positive carcinoma of the cervix. Int J Cancer 69: 159–164.PubMedGoogle Scholar
  77. 77.
    Gregoire L, Lawrence D, Kukuruga D, et al. (1994) Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women. Int J Cancer 57: 504–507.PubMedGoogle Scholar
  78. 78.
    Neuman RJ, Huettner PC, Li L, et al. (2000) Association between DQB1 and cervical cancer in patients with human papillomavirus and family controls. Obstet Gynecol 95: 134–140.PubMedGoogle Scholar
  79. 79.
    Odunsi K, Terry G, Ho L, et al. (1995) Association between HLA DQB1*03 and cervical intra-epithelial neoplasia. Mol Med 1: 161–171.PubMedGoogle Scholar
  80. 80.
    Odunsi K, Terry G, Ho L, et al. (1996) Susceptibility to human papillomavirus-associated cervical intra-epithelial neoplasia is determined by specific HLA DR-DQ alleles. Int J Cancer 67: 595–602.PubMedGoogle Scholar
  81. 81.
    Vandenvelde C, De Foor M, Van Beers D (1993) HLA-DQB1*03 and cervical intraepithelial neoplasia grades I–III. Lancet 341: 442–443.PubMedGoogle Scholar
  82. 82.
    David ALM, Taylor GM, Gokhale D, et al. (1992) HLA-DQB1*03 and cervical intraepithelial neoplasia type III. Lancet 340: 52.PubMedGoogle Scholar
  83. 83.
    Apple RJ, Erlich HA, Klitz W, et al. (1994) HLA DR-DQ associations with cervical carcinoma show papillomavirus-type specificity. Nat Genet 6: 157–162.PubMedGoogle Scholar
  84. 84.
    Wank R, Meulen J, Luande J, et al. (1993) Cervical intraepithelial neoplasia, cervical carcinoma, and risk for patients with HLA-DQB1 *0602, *301, *0303 alleles. Lancet 341: 1215.PubMedGoogle Scholar
  85. 85.
    Sanjeevi CB, HjelmstrÖm P, Hallmans G, et al. (1996) Different HLA-DR-DQ haplotypes are associated with cervical intraepithelial neoplasia among human papillomavirus type-16 seropositive and seronegative Swedish women. Int J Cancer 68: 409–414.PubMedGoogle Scholar
  86. 86.
    Helland Å, Olsen AO, GjØen K, et al. (1998) An increased risk of cervical intra-epithelial neoplasia grade II–III among human papillomavirus positive patients with the HLA-DQA1*0102-DQB1*0602 haplotype; a population-based case–control study of Norwegian women. Int J Cancer 76: 19–24.PubMedGoogle Scholar
  87. 87.
    Apple RJ, Becker TM, Wheeler CM, et al. (1995) Comparison of human leukocyte antigen DR-DQ disease associations found with cervical dysplasia and invasive cervical carcinoma. J Natl Cancer Inst 87: 427–436.PubMedGoogle Scholar
  88. 88.
    Engelmark M, Beskow A, Magnusson J, et al. (2004) Affected sib-pair analysis of the contribution of HLA class I and class II loci to development of cervical cancer. Hum Mol Genet 13: 1951–1958.PubMedGoogle Scholar
  89. 89.
    Beskow AH, Engelmark MT, Magnusson JJ, et al. (2005) Interaction of host and viral risk factors for development of cervical carcinoma in situ. Int J Cancer 117: 690–692.PubMedGoogle Scholar
  90. 90.
    Allen M, Kalantari M, Ylitalo N, et al. (1996) HLA DQ-DR haplotype and susceptibility to cervical carcinoma: indications of increased risk for development of cervical carcinoma in individuals infected with HPV 18. Tissue Antigens 48: 32–37.PubMedGoogle Scholar
  91. 91.
    Glew SS, Duggan-Keen M, Ghosh AK, et al. (1993) Lack of association of HLA polymorphisms with human papillomavirus-related cervical cancer. Hum Immunol 37: 157–164.PubMedGoogle Scholar
  92. 92.
    Glew SS, Stern PL (1992) HLA antigens and cervical carcinoma. Nature 356: 22.PubMedGoogle Scholar
  93. 93.
    Koopman LA, Corver WE, van der Slik AR, et al. (2000) Multiple genetic alterations cause frequent and heterogeneous human histocompatibility leukocyte antigen class I loss in cervical cancer. J Exp Med 191: 961–976.PubMedGoogle Scholar
  94. 94.
    Wang SS, Hildesheim A, Gao X, et al. (2002) Comprehensive analysis of human leukocyte antigen class I alleles and cervical neoplasia in 3 epidemiologic studies. J Infect Dis 186: 598–605.PubMedGoogle Scholar
  95. 95.
    Carrington M, Wang S, Martin MP, et al. (2005) Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. J Exp Med 201: 1069–1075.PubMedGoogle Scholar
  96. 96.
    Deshpande A, Wheeler CM, Hunt WC, et al. (2008) Variation in HLA class I antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer. J Infect Dis 197: 371–381.PubMedGoogle Scholar
  97. 97.
    Gostout BS, Poland GA, Giuntoli RL, et al. (2001) HLA DR, TAP2, and TNFα polymorphisms are associated with cervix cancer risk. Gynecol Oncol 80: 280.Google Scholar
  98. 98.
    Deshpande A, Nolan JP, White PS, et al. (2005) TNF-alpha promoter polymorphisms and susceptibility to human papillomavirus 16-associated cervical cancer. J Infect Dis 191: 969–976.PubMedGoogle Scholar
  99. 99.
    Duarte I, Santos A, Sousa H, et al. (2005) G-308A TNF-alpha polymorphism is associated with an increased risk of invasive cervical cancer. Biochem Biophys Res Commun 334: 588–592.PubMedGoogle Scholar
  100. 100.
    Calhoun ES, McGovern RM, Janney CA, et al. (2002) Host genetic polymorphism analysis in cervical cancer. Clin Chem 48: 1218–1224.PubMedGoogle Scholar
  101. 101.
    Jang WH, Yang YI, Yea SS, et al. (2001) The -238 tumor necrosis factor-alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett 166: 41–46.PubMedGoogle Scholar
  102. 102.
    Ghaderi M, Nikitina L, Peacock CS, et al. (2000) Tumor necrosis factor a-11 and DR15-DQ6 (B*0602) haplotype increase the risk for cervical intraepithelial neoplasia in human papillomavirus 16 seropositive women in Northern Sweden. Cancer Epidemiol Biomarkers Prev 9: 1067–1070.PubMedGoogle Scholar
  103. 103.
    Ghaderi M, Nikitina Zake L, Wallin K, et al. (2001) Tumor necrosis factor A and MHC class I chain related gene A (MIC-A) polymorphisms in Swedish patients with cervical cancer. Hum Immunol 62: 1153–1158.PubMedGoogle Scholar
  104. 104.
    Shrestha S, Wang C, Aissani B, et al. (2007) Interleukin-10 gene (IL10) polymorphisms and human papillomavirus clearance among immunosuppressed adolescents. Cancer Epidemiol Biomarkers Prev 16: 1626–1632.PubMedGoogle Scholar
  105. 105.
    Farzaneh F, Roberts S, Mandal D, et al. (2006) The IL-10-1082G polymorphism is associated with clearance of HPV infection. BJOG 113: 961–964.PubMedGoogle Scholar
  106. 106.
    Ivansson EL, Gustavsson IM, Magnusson JJ, et al. (2007) Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer. Int J Cancer 121: 2451–2457.PubMedGoogle Scholar
  107. 107.
    Stanczuk GA, Sibanda EN, Perrey C, et al. (2001) Cancer of the uterine cervix may be significantly associated with a gene polymorphism coding for increased IL-10 production. Int J Cancer 94: 792–794.PubMedGoogle Scholar
  108. 108.
    Zoodsma M, Nolte IM, Schipper M, et al. (2005) Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. Int J Gynecol Cancer 15 Suppl 3: 282–290.PubMedGoogle Scholar
  109. 109.
    Sun T, Zhou Y, Li H, et al. (2005) FASL -844C polymorphism is associated with increased activation-induced T cell death and risk of cervical cancer. J Exp Med 202: 967–974.PubMedGoogle Scholar
  110. 110.
    Ueda M, Hung YC, Terai Y, et al. (2005) Fas gene promoter -670 polymorphism (A/G) is associated with cervical carcinogenesis. Gynecol Oncol 98: 129–133.PubMedGoogle Scholar
  111. 111.
    Ueda M, Terai Y, Kanda K, et al. (2006) Fas gene promoter -670 polymorphism in gynecological cancer. Int J Gynecol Cancer 16 Suppl 1: 179–182.PubMedGoogle Scholar
  112. 112.
    Lai HC, Lin WY, Lin YW, et al. (2005) Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis: An analysis of haplotype and gene–gene interaction. Gynecol Oncol 99: 113–118.PubMedGoogle Scholar
  113. 113.
    Zhang Z, Borecki I, Nguyen L, et al. (2007) CD83 gene polymorphisms increase susceptibility to human invasive cervical cancer. Cancer Res 67: 11202–11208.PubMedGoogle Scholar
  114. 114.
    Dumont P, Leu JI, Della Pietra AC, 3rd, et al. (2003) The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33: 357–365.PubMedGoogle Scholar
  115. 115.
    Matlashewski GJ, Tuck S, Pim D, et al. (1987) Primary structure polymorphism at amino acid residue 72 of human p53. Mol Cell Biol 7: 961–963.PubMedGoogle Scholar
  116. 116.
    Walker KK, Levine AJ (1996) Identification of a novel p53 functional domain that is necessary for efficient growth suppression. Proc Natl Acad Sci USA 93: 15335–15340.PubMedGoogle Scholar
  117. 117.
    Storey A, Thomas M, Kalita A, et al. (1998) Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393: 229–234.PubMedGoogle Scholar
  118. 118.
    Jee SH, Won SY, Yun JE, et al. (2004) Polymorphism p53 codon-72 and invasive cervical cancer: a meta-analysis. Int J Gynaecol Obstet 85: 301–308.PubMedGoogle Scholar
  119. 119.
    Koushik A, Platt RW, Franco EL (2004) p53 codon 72 polymorphism and cervical neoplasia: a meta-analysis review. Cancer Epidemiol Biomarkers Prev 13: 11–22.PubMedGoogle Scholar
  120. 120.
    Sousa H, Santos AM, Pinto D, et al. (2007) Is the p53 codon 72 polymorphism a key biomarker for cervical cancer development? A meta-analysis review within European populations. Int J Mol Med 20: 731–741.PubMedGoogle Scholar
  121. 121.
    Beckman G, Girgander R, Sjalander A, et al. (1994) Is p53 polymorphism maintained by natural selection? Hum Hered 44: 266–270.PubMedGoogle Scholar
  122. 122.
    Funk JO, Waga S, Harry JB, et al. (1997) Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV 16 E7 oncoprotein. Genes Dev 11: 2090–2100.PubMedGoogle Scholar
  123. 123.
    Zerfass-Thome K, Zwerschke W, Mannhardt B, et al. (1996) Inactivation of the cdk inhibitor p27KIP1 by the human papillomavirus type 16 E7 oncoprotein. Oncogene 13: 2323–2330.PubMedGoogle Scholar
  124. 124.
    Roh JW, Kim MH, Kim JW, et al. (2001) Polymorphisms in codon 31 of p21 and cervical cancer susceptibility in Korean women. Cancer Lett 165: 59–62.PubMedGoogle Scholar
  125. 125.
    Lee JE, Lee SJ, Namkoong SE, et al. (2004) Gene–gene and gene–environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer. Int J Gynecol Cancer 14: 118–125.PubMedGoogle Scholar
  126. 126.
    Betticher DC, Thatcher N, Altermatt HJ, et al. (1995) Alternate splicing produces a novel cyclin D1 transcript. Oncogene 11: 1005–1011.PubMedGoogle Scholar
  127. 127.
    Catarino R, Matos A, Pinto D, et al. (2005) Increased risk of cervical cancer associated with cyclin D1 gene A870G polymorphism. Cancer Genet Cytogenet 160: 49–54.PubMedGoogle Scholar
  128. 128.
    Jeon YT, Kim JW, Song JH, et al. (2005) Cyclin D1 G870A polymorphism and squamous cell carcinoma of the uterine cervix in Korean women. Cancer Lett 223: 259–263.PubMedGoogle Scholar
  129. 129.
    Pasche B, Knobloch TJ, Bian Y, et al. (2005) Somatic acquisition and signaling of TGFBR1*6A in cancer. JAMA 294: 1634–1646.PubMedGoogle Scholar
  130. 130.
    Weghorst CM, Ferguson JM, Knobloch TJ, et al. (2008) Cancer susceptibility polymorphisms in transforming growth factor beta receptor 1 (TGFBR1) are increased in cervical cancer and CINIII. Gynecol Oncol 108: S85.Google Scholar
  131. 131.
    Goodman MT, McDuffie K, Hernandez B, et al. (2001) Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia. Cancer Epidemiol Biomarkers Prev 10: 1275–1280.PubMedGoogle Scholar
  132. 132.
    Piyathilake CJ, Macaluso M, Johanning GL, et al. (2000) Methylenetetrahydrofolate reductase (MTHFR) polymorphism increases the risk of cervical intraepithelial neoplasia. Anticancer Res 20: 1751–1758.PubMedGoogle Scholar
  133. 133.
    Henao OL, Piyathilake CJ, Waterbor JW, et al. (2005) Women with polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are less likely to have cervical intraepithelial neoplasia (CIN) 2 or 3. Int J Cancer 113: 991–997.PubMedGoogle Scholar
  134. 134.
    Piyathilake CJ, Azrad M, Macaluso M, et al. (2007) Protective association of MTHFR polymorphism on cervical intraepithelial neoplasia is modified by riboflavin status. Nutrition 23: 229–235.PubMedGoogle Scholar
  135. 135.
    Zoodsma M, Nolte IM, Schipper M, et al. (2005) Methylenetetrahydrofolate reductase (MTHFR) and susceptibility for (pre)neoplastic cervical disease. Hum Genet 116: 247–254.PubMedGoogle Scholar
  136. 136.
    Gerhard DS, Nguyen LT, Zhang ZY, et al. (2003) A relationship between methylenetetrahydrofolate reductase variants and the development of invasive cervical cancer. Gynecol Oncol 90: 560–565.PubMedGoogle Scholar
  137. 137.
    Lambropoulos AF, Agorastos T, Foka ZJ, et al. (2003) Methylenetetrahydrofolate reductase polymorphism C677T is not associated to the risk of cervical dysplasia. Cancer Lett 191: 187–191.PubMedGoogle Scholar
  138. 138.
    Rao GG, Kurien A, Gossett D, et al. (2006) A case–control study of methylenetetrahydrofolate reductase polymorphisms in cervical carcinogenesis. Gynecol Oncol 101: 250–254.PubMedGoogle Scholar
  139. 139.
    Flanagan JM (2007) Host epigenetic modifications by oncogenic viruses. Br J Cancer 96: 183–188.PubMedGoogle Scholar
  140. 140.
    Burgers WA, Blanchon L, Pradhan S, et al. (2007) Viral oncoproteins target the DNA methyltransferases. Oncogene 26: 1650–1655.PubMedGoogle Scholar
  141. 141.
    Brehm A, Nielsen SJ, Miska EA, et al. (1999) The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. Embo J 18: 2449–2458.PubMedGoogle Scholar
  142. 142.
    Patel D, Huang SM, Baglia LA, et al. (1999) The E6 protein of human papillomavirus type 16 binds to and inhibits co-activation by CBP and p300. Embo J 18: 5061–5072.PubMedGoogle Scholar
  143. 143.
    Sova P, Feng Q, Geiss G, et al. (2006) Discovery of novel methylation biomarkers in cervical carcinoma by global demethylation and microarray analysis. Cancer Epidemiol Biomarkers Prev 15: 114–123.PubMedGoogle Scholar
  144. 144.
    Wang SS, Smiraglia DJ, Wu Y-Z, et al. (2008) Identification of novel methylation markers in cervical cancer using restriction landmark genomic scanning (RLGS). Cancer Res 68: 2489–2497.PubMedGoogle Scholar
  145. 145.
    Feng Q, Balasubramanian A, Hawes SE, et al. (2005) Detection of hypermethylated genes in women with and without cervical neoplasia. J Natl Cancer Inst 97: 273–282.PubMedGoogle Scholar
  146. 146.
    Henken FE, Wilting SM, Overmeer RM, et al. (2007) Sequential gene promoter methylation during HPV-induced cervical carcinogenesis. Br J Cancer 97: 1457–1464.PubMedGoogle Scholar
  147. 147.
    Steenbergen RD, Kramer D, Braakhuis BJ, et al. (2004) TSLC1 gene silencing in cervical cancer cell lines and cervical neoplasia. J Natl Cancer Inst 96: 294–305.PubMedGoogle Scholar
  148. 148.
    Li J, Zhang Z, Bidder M, et al. (2005) IGSF4 promoter methylation and expression silencing in human cervical cancer. Gynecol Oncol 96: 150–158.PubMedGoogle Scholar
  149. 149.
    Shivapurkar N, Sherman ME, Stastny V, et al. (2007) Evaluation of candidate methylation markers to detect cervical neoplasia. Gynecol Oncol 107: 549–553.PubMedGoogle Scholar
  150. 150.
    Ivanova T, Petrenko A, Gritsko T, et al. (2002) Methylation and silencing of the retinoic acid receptor-beta 2 gene in cervical cancer. BMC Cancer 2: 4.PubMedGoogle Scholar
  151. 151.
    Virmani AK, Muller C, Rathi A, et al. (2001) Aberrant methylation during cervical carcinogenesis. Clin Cancer Res 7: 584–589.PubMedGoogle Scholar
  152. 152.
    Dong SM, Kim HS, Rha SH, et al. (2001) Promoter hypermethylation of multiple genes in carcinoma of the uterine cervix. Clin Cancer Res 7: 1982–1986.PubMedGoogle Scholar
  153. 153.
    Kang S, Kim JW, Kang GH, et al. (2006) Comparison of DNA hypermethylation patterns in different types of uterine cancer: cervical squamous cell carcinoma, cervical adenocarcinoma and endometrial adenocarcinoma. Int J Cancer 118: 2168–2171.PubMedGoogle Scholar
  154. 154.
    Shivapurkar N, Toyooka S, Toyooka KO, et al. (2004) Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer 109: 786–792.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Department of GeneticsWashington University School of MedicineSt. LouisUSA

Personalised recommendations