Association Between HLA DQBl * 03 and Cervical Intra-epithelial Neoplasia
Tóm tắt
Cervical intraepithelial neoplasia (CIN) and cervical cancer have been shown to be strongly associated with infection by human papillomavirus (HPV). However, other factors may be contributory in the progression from normal epithelium to CIN and cervical cancer, since not all women with HPV infection develop disease. Recently, it was demonstrated that there is a high risk for cervical cancer and CIN in women with HLA DQB1 * 03 (RR = 7.1, p < 0.0009) (1). Subsequent reports have been conflicting, due to sample size, genetic heterogeneity and differences in the techniques employed for the detection of HLA DQB1 * 03. DNA from cervical smears of 178 women with CIN and 420 controls with normal cervical cytology was analyzed by polymerase chain reaction (PCR) with type-specific primers for HPV 16, 18, 31, and 33. The DNA from test and control samples were also analyzed by a novel PCR technique, which mutates the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme Mlu I that distinguish DQB1 * 03 from other alleles and are confirmed by digestion of amplified DNA with Mlu I. Further analysis of individual DQB1 * 03 alleles was performed using PCR and allele-specific primers. One hundred forty-four (34%) out of 420 controls (all HPV 16, 18, 31, or 33 negative and normal cytology), 37/66 (56%) of CIN I and 72/112 (64%) of CIN III were positive for DQB1 * 03 (trend test, p < 0.001, χ2 = 37.3). A significant association was observed between DQB1 * 03 and CIN (odds ratio 3.03; 95% CI 2.11–3.45). Of women with CIN, 131/ 178 (73.5%) had HPV (types 16, 18, 31, or 33) infection. There was a significant association between DQB1 * 03 and presence of HPV (odds ratio 3.43; 95% CI 2.25–5.10). Homozygosity for DQB1 * 03 was more strongly associated with CIN than heterozygosity (odds ratios 4.0 and 2.63, respectively); and for the presence of HPV (odds ratio 4.47; 95% CI 2.58–7.77). HLA DQB1 * 0301 was the most strongly associated allele with CIN and HPV (odds ratios 2.53 and 2.63, respectively). HLA DQB1 * 03 is associated significantly with CIN and may be permissive for HPV infection. Further analysis of class II HLA typing in CIN is necessary to evaluate this association.
Tài liệu tham khảo
Wank R, Thomssen C. (1991) High risk of squamous cell carcinoma of the cervix for women with HLA-DQw3. Nature 352: 723–725.
Meijer CJLM, van den Brule AJC, Snijders PJF, Heimerhorst T, Kenemans P, Walboomers JMM. (1992) Detection of human papillomavirus in cervical scrapes by the polymerase chain reaction in relation to cytology: Possible implications for cervical cancer screening. In: Munoz N, Bosch FX, Shah KV, Meheus A (eds). The Epidemiology of Human Papillomavirus and Cervical Cancer. Oxford University Press, Oxford.
Lorincz AT, Reid R, Jenson B, Greenberg MD, Lancaster W, Kurman RJ. (1992) Human papillomavirus infection of the cervix: relative risk association of 15 common anogenital types. Obstet. Gynecol. 79: 328–337.
Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT. (1989) HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. E.M.B.O. J. 8: 3905–3910.
Munger K, Phelps WC, Bubb V, Howley PM, Schlegel RM. (1989) The E6 and E7 genes of human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J. Virol. 63: 4417–4421.
Vousden KH. (1993) Interactions of human papillomavirus transforming proteins with the products of tumour suppresor genes. F.A.S.E.B. J. 7: 872–879.
Cuzick J, Terry G, Ho L, Hollingworth T, Anderson M. (1992) Human papillomavirus type 16 DNA in cervical smears as a predictor of high-grade cervical intraepithelial neoplasia. Lancet 339: 959–960.
Cuzick J, Terry G, Ho L, Hollingworth T, Anderson M. (1994) Type-specific human papillomavirus DNA in abnormal smears as a predictor of high-grade cervical intraepithelial neoplasia. Br. J. Cancer 69: 167–171.
Richart RM. (1987) Causes and management of cervical intraepithelial neoplasia. Cancer 60: 1951–1959.
Anderson M, Brown C, Buckley C, et al. (1991) Current views on cervical intraepithelial neoplasia. J. Clin. Pathol. 44: 969–978.
Mehal WZ, Lo YD, Herrington S, et al. (in press) Human papillomavirus infection plays an important role in determining the HLA associated risk of cervical carcinogenesis. J. Clin. Pathol.
Olerup O, Aldener A, Fogdell A. (1993) HLA-DQB1 and -DQA1 typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours. Tissue Antigens 41: 119–134.
Davis W, Breslow NE Day NE (eds). (1980) Statistical Methods in Cancer Research: vol.1: The analysis of case control studies. International Agency for Research on Cancer, Lyon.
Armitage P (ed). (1971) Statistical Methods in Medical Research. Blackwell, Oxford.
Parkin DM, Laara E, Muir CS. (1988) Estimates of the worldwide frequency of sixteen major cancers in 1980. Int. J. Cancer 41: 184–197.
Schiffman MH, Bauer HM, Hoover RN, et al. (1993) Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl. Cancer Inst. 85: 958–964.
Walboomers J, Melkert P, van den Brule A, Snijders P, Meijer C. (1992) The polymerase chain reaction for screening in diagnostic cytopathology of the cervix. In: Herrington CS, McGee JO (eds). Diagnostic Molecular Pathology. IRL press, Oxford.
Schneider A, Koutsky L. (1992) Natural history and epidemiological features of genital HPV infection. In: Munoz M, Bosch FX, Shah KV, Meheus A (eds). The Epidemiology of Cervical Cancer and Human Papillomavirus. International Agency for Research on Cancer, Lyon.
Zur Hausen H. (1986) Intracellular surveillance of persisting viral infections. Lancet 1: 489–491.
Zur Hausen H. (1991) Viruses in human cancers. Science 254: 1167–1173.
Sillman FH, Sedlis A. (1987) Anogenital papillomavirus infection and neoplasia in immunodeficient women. In: Reed R (ed). Human Papillomavirus. W. B. Saunders, Philadelphia.
Schafer A, Friemann W, Mielke M, Schwatlander B, Koch MA. (1991) The increased frequency of cervical dysplasia in women infected with the human immunodeficiency virus is related to the degree of immunosuppression. Am. J. Obstet. Gynecol. 164: 593–599.
Connor MF, Stern PL. (1990) Loss of MHC class I expression in cervical carcinomas. Int. J. Cancer 46: 1029–1034.
Glew SS, Duggan-Keen M, Cabrera T, Stern PL. (1992) HLA class II antigen expression in human papillomavirus-associated cervical cancer. Cancer Res. 52: 4009–4016.
Mytilineos J, Scherer S, Opelz G. (1990) Comparison of RFLP-DR-Beta and serological HLA-DR typing in 1500 individuals. Transplantation 50: 870–873.
Heiland A, Borresen AL, Kaern J, Ronningen KS, Thorsby E. (1992) HLA antigens and cervical carcinoma. Nature 356: 23.
Apple RJ, Erlich HA, Klitz W, Manos MM, Becker TM, Wheeler CM. (1992) HLA DR-DQ associations with cervical carcinoma show papilloma virus-type specificity. Nature Gen. 6: 157–162.
Vandenvelde C, deFoor M, vanBeers D. (1993) HLA-DQB1 * 03 and cervical intraepithelial neoplasia grades I–III. Lancet 341: 442–444.
David ALM, Taylor GM, Gokhale D, Aplin JD, Seif MW, Tindall VR. (1992) HLA-DQB1 * 03 and cervical intraepithelial neoplasia type III. Lancet 340: 52.
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.
Gregoire L, Lawrence WD, Kukuruga D, Eisenbrey AB, Lancester WD. (1994) Association between HLA-DQB1 alleles and risk for cervical cancer in African-American women. Int. J. Cancer 57: 504–507.
Wank R, Meulen JT, Luande J, Eberhardt H-C, Pawlita M. (1993) Cervical intraepithelial neoplasia, cervical carcinoma, and risk for patients with HLA-DQB1 * 0602, *301, *0303 alleles. Lancet 341: 1215.
Bonagura VR, O’Reilly ME, Abramson AL, Steinberg BM. (1993) Recurrent respiratory papillomatosis (RRP): Enriched HLA DQw3 phenotype and decreased class I MHC expression. Proceedings of the 12th International Papillomavirus Conference. p. 48.
Han R, Breitburd F, Marche PN, Orth G. (1992) Linkage of regression and malignant conversion of rabbit viral papillomas to MHC class II genes. Nature 356: 66–68.
Mellins E, Woefel M, Pious D. (1987) Importance of HLA-DQ and HLA-DP restriction elements in T-cell responses to soluble antigens—Mutational analysis. Hum. Immunol 18: 211–213.
Altman DM, Sansom D, Marsh SGE. (1991) What is the basis for HLA-DQ associations with autoimmune disease? Immunol. Today 12: 267–270.
Ishikura H, Ishikawa N, Aizawa M. (1987) Differential expression of HLA class H antigens in the human thymus-relative paucity of HLA-DQ antigens in the thymic medulla. Transplantation 44: 314–317.
Nishimura Y, Sasazuki T. (1983) Suppressor T cells control the HLA-linked low responsiveness to streptococcal antigen in man. Nature 301: 67.
Sasazuki T, Ohta N, Kaneoka R, Kojima S. (1980) Association between an HLA haplotype and low responsiveness to schistosomal worm antigen in man. J. Exp. Med. 152: 314.
Ottenhoff THM, Walford C, Nishimura Y, Reddy NBB, Sasazuki T. (1990) HLA DQ molecules and the control of mycobaterium leprae specific T cell non responsiveness in lepromatous leprosy patients. Eur. J. Immunol. 20: 2347.
Sasazuki T, Kohno Y, Iwamoto I, Tanimura M, Naito S. (1978) Association between an HLA haplotype and low responsiveness to tetanus toxoid in man. Nature 272: 359.
Hatae K, Kimura A, Okubo R, et al. (1992) Genetic control of non responsiveness to hepatitis B virus vaccine by an extended HLA haplotype. Eur. J. Immunol. 22: 1899–1905.
Salgame P, Convit J, Bloom BR. (1991) Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted. Proc. Natl. Acad. Sci. U.S.A. 88: 2598–2602.
Sasazuki T, Kikuchi K, Hirayama S, Matsushita S, Ohta N, Nishimura Y. (1989) HLA-linked immune suppression in humans. Immunology S2: 21–25.
Chen L, Thomas EK, Hu SL, Hellstrom J, Hellstrom KE. (1991) Human papillomavirus type 16 nucleoprotein E7 is a tumour rejection antigen. Proc. Natl Acad. Sci. U.S.A. 88: 110–114.