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British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Oct;85(8):1153–1156. doi: 10.1054/bjoc.2001.2085

The significance of p53 codon 72 polymorphism for the development of cervical adenocarcinomas

S Andersson 1, E Rylander 2, A Strand 3, J Sällström 4, E Wilander 4
PMCID: PMC2375157  PMID: 11710828

Abstract

Infection with the human papillomavirus is an important co-factor in the development of cervical carcinomas. Accordingly, HPV DNA is recognised in most of these tumours. Polymorphism of the p53 gene, codon 72, is also considered a risk factor in the development of cervical carcinoma. However, this finding is contradicted by several observers. In the present investigation, 111 cases of adenocarcinoma of the cervix collected through the Swedish Cancer Registry and 188 controls (females with normal cytology at organised gynaecological screening) were analysed with regard to p53, codon 72, polymorphism using a PCR- and SSCP-based technique. In the controls, 9% showed pro/pro, 44% pro/arg and 47% arg/arg, whereas in the invasive adenocarcinomas, the corresponding figures were 0%, 29% and 71%, respectively. The difference was statistically significant (P = 0.001). HPV DNA was identified in 86 tumours (HPV 18 in 48, HPV 16 in 31 and HPV of unknown type in 7 cases) and 25 tumours were HPV negative. The p53, codon 72, genotypes observed in HPV-positive and HPV-negative cervical adenocarcinomas were not statistically different (P = 0.690). The results indicate that women homozygotic for arg/arg in codon 72 of the p53 gene are at an increased risk for the development of cervical adenocarcinomas. However, this genetic disposition seems to be unrelated to the HPV infection. © 2001 Cancer Research Campaign  http://www.bjcancer.com

Keywords: cervix, adenocarcinomas, HPV-infection, p53, polymorphism

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Selected References

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  1. Agorastos T., Lambropoulos A. F., Constantinidis T. C., Kotsis A., Bontis J. N. p53 codon 72 polymorphism and risk of intra-epithelial and invasive cervical neoplasia in Greek women. Eur J Cancer Prev. 2000 Apr;9(2):113–118. doi: 10.1097/00008469-200004000-00007. [DOI] [PubMed] [Google Scholar]
  2. Alemi M., Andersson S., Sällström J., Wilander E. Rapid test for identification of a human papillomavirus 16 E6 L83V variant. Diagn Mol Pathol. 1999 Jun;8(2):97–100. doi: 10.1097/00019606-199906000-00006. [DOI] [PubMed] [Google Scholar]
  3. Andersson S., Alemi M., Rylander E., Strand A., Larsson B., Sällström J., Wilander E. Uneven distribution of HPV 16 E6 prototype and variant (L83V) oncoprotein in cervical neoplastic lesions. Br J Cancer. 2000 Aug;83(3):307–310. doi: 10.1054/bjoc.2000.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andersson S., Rylander E., Larsson B., Strand A., Silfversvärd C., Wilander E. The role of human papillomavirus in cervical adenocarcinoma carcinogenesis. Eur J Cancer. 2001 Jan;37(2):246–250. doi: 10.1016/s0959-8049(00)00376-2. [DOI] [PubMed] [Google Scholar]
  5. Bergström R., Sparén P., Adami H. O. Trends in cancer of the cervix uteri in Sweden following cytological screening. Br J Cancer. 1999 Sep;81(1):159–166. doi: 10.1038/sj.bjc.6690666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brooks L. A., Tidy J. A., Gusterson B., Hiller L., O'Nions J., Gasco M., Marin M. C., Farrell P. J., Kaelin W. G., Jr, Crook T. Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus. Cancer Res. 2000 Dec 15;60(24):6875–6877. [PubMed] [Google Scholar]
  7. Hildesheim A., Schiffman M., Brinton L. A., Fraumeni J. F., Jr, Herrero R., Bratti M. C., Schwartz P., Mortel R., Barnes W., Greenberg M. p53 polymorphism and risk of cervical cancer. Nature. 1998 Dec 10;396(6711):531–532. doi: 10.1038/25040. [DOI] [PubMed] [Google Scholar]
  8. Iwasawa A., Nieminen P., Lehtinen M., Paavonen J. Human papillomavirus DNA in uterine cervix squamous cell carcinoma and adenocarcinoma detected by polymerase chain reaction. Cancer. 1996 Jun 1;77(11):2275–2279. doi: 10.1002/(SICI)1097-0142(19960601)77:11<2275::AID-CNCR14>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  9. Josefsson A. M., Magnusson P. K., Ylitalo N., Quarforth-Tubbin P., Pontén J., Adami H. O., Gyllensten U. B. p53 polymorphism and risk of cervical cancer. Nature. 1998 Dec 10;396(6711):531–532. doi: 10.1038/25037. [DOI] [PubMed] [Google Scholar]
  10. Lungu O., Wright T. C., Jr, Silverstein S. Typing of human papillomaviruses by polymerase chain reaction amplification with L1 consensus primers and RFLP analysis. Mol Cell Probes. 1992 Apr;6(2):145–152. doi: 10.1016/0890-8508(92)90059-7. [DOI] [PubMed] [Google Scholar]
  11. Makni H., Franco E. L., Kaiano J., Villa L. L., Labrecque S., Dudley R., Storey A., Matlashewski G. P53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: effect of inter-laboratory variation. Int J Cancer. 2000 Aug 15;87(4):528–533. [PubMed] [Google Scholar]
  12. Miller B. E., Flax S. D., Arheart K., Photopulos G. The presentation of adenocarcinoma of the uterine cervix. Cancer. 1993 Aug 15;72(4):1281–1285. doi: 10.1002/1097-0142(19930815)72:4<1281::aid-cncr2820720421>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  13. Minaguchi T., Kanamori Y., Matsushima M., Yoshikawa H., Taketani Y., Nakamura Y. No evidence of correlation between polymorphism at codon 72 of p53 and risk of cervical cancer in Japanese patients with human papillomavirus 16/18 infection. Cancer Res. 1998 Oct 15;58(20):4585–4586. [PubMed] [Google Scholar]
  14. Mählck C. G., Jonsson H., Lenner P. Pap smear screening and changes in cervical cancer mortality in Sweden. Int J Gynaecol Obstet. 1994 Mar;44(3):267–272. doi: 10.1016/0020-7292(94)90177-5. [DOI] [PubMed] [Google Scholar]
  15. Rosenthal A. N., Ryan A., Al-Jehani R. M., Storey A., Harwood C. A., Jacobs I. J. p53 codon 72 polymorphism and risk of cervical cancer in UK. Lancet. 1998 Sep 12;352(9131):871–872. doi: 10.1016/S0140-6736(98)07357-7. [DOI] [PubMed] [Google Scholar]
  16. Saiki R. K., Chang C. A., Levenson C. H., Warren T. C., Boehm C. D., Kazazian H. H., Jr, Erlich H. A. Diagnosis of sickle cell anemia and beta-thalassemia with enzymatically amplified DNA and nonradioactive allele-specific oligonucleotide probes. N Engl J Med. 1988 Sep 1;319(9):537–541. doi: 10.1056/NEJM198809013190903. [DOI] [PubMed] [Google Scholar]
  17. Storey A., Thomas M., Kalita A., Harwood C., Gardiol D., Mantovani F., Breuer J., Leigh I. M., Matlashewski G., Banks L. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998 May 21;393(6682):229–234. doi: 10.1038/30400. [DOI] [PubMed] [Google Scholar]
  18. Tenti P., Pavanello S., Padovan L., Spinillo A., Vesentini N., Zappatore R., Migliora P., Zara C., Ranzani G. N., Carnevali L. Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix. Am J Pathol. 1998 Apr;152(4):1057–1063. [PMC free article] [PubMed] [Google Scholar]
  19. Tenti P., Romagnoli S., Silini E., Zappatore R., Spinillo A., Giunta P., Cappellini A., Vesentini N., Zara C., Carnevali L. Human papillomavirus types 16 and 18 infection in infiltrating adenocarcinoma of the cervix: PCR analysis of 138 cases and correlation with histologic type and grade. Am J Clin Pathol. 1996 Jul;106(1):52–56. doi: 10.1093/ajcp/106.1.52. [DOI] [PubMed] [Google Scholar]
  20. Vizcaino A. P., Moreno V., Bosch F. X., Muñoz N., Barros-Dios X. M., Parkin D. M. International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer. 1998 Feb 9;75(4):536–545. doi: 10.1002/(sici)1097-0215(19980209)75:4<536::aid-ijc8>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  21. Walboomers J. M., Jacobs M. V., Manos M. M., Bosch F. X., Kummer J. A., Shah K. V., Snijders P. J., Peto J., Meijer C. J., Muñoz N. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999 Sep;189(1):12–19. doi: 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  22. Zehbe I., Sällström J. F., Evander M., Edlund K., Rylander E., Wadell G., Wilander E. Nonradioisotopic detection and typing of human papillomaviruses by use of polymerase chain reaction and single-strand conformation polymorphism. Diagn Mol Pathol. 1996 Sep;5(3):206–213. doi: 10.1097/00019606-199609000-00010. [DOI] [PubMed] [Google Scholar]
  23. Zehbe I., Wilander E., Delius H., Tommasino M. Human papillomavirus 16 E6 variants are more prevalent in invasive cervical carcinoma than the prototype. Cancer Res. 1998 Feb 15;58(4):829–833. [PubMed] [Google Scholar]
  24. Zehbe I., Wilander E. Human papillomavirus infection and invasive cervical neoplasia: a study of prevalence and morphology. J Pathol. 1997 Mar;181(3):270–275. doi: 10.1002/(SICI)1096-9896(199703)181:3<270::AID-PATH767>3.0.CO;2-R. [DOI] [PubMed] [Google Scholar]
  25. Zehbe I., Wilander E. Nonisotopic ELISA-based detection of human papillomavirus-amplified DNA. Mod Pathol. 1997 Mar;10(3):188–191. [PubMed] [Google Scholar]
  26. de Roda Husman A. M., Walboomers J. M., van den Brule A. J., Meijer C. J., Snijders P. J. The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. J Gen Virol. 1995 Apr;76(Pt 4):1057–1062. doi: 10.1099/0022-1317-76-4-1057. [DOI] [PubMed] [Google Scholar]

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