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A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese

  • Original Paper
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Journal of Biomedical Science

Abstract

An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53–1.88] and 2.80 (95% CI 1.04–7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or ≥7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13–1.00, p=0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075–0.84, p=0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13–1.30, p=0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004–0.89, p=0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.

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References

  1. Brothman AR. Cytogenetics and molecular genetics of cancer of the prostate. Am J Med Genet 115:150–156;2002.

    Article  PubMed  Google Scholar 

  2. Frebourg T, Friend SH. The importance of p53 gene alterations in human cancer: Is there more than circumstantial evidence? J Natl Cancer Inst 85:1554–1557;1993.

    PubMed  Google Scholar 

  3. Gumerlock PH, Chi SG, Shi XB, Voeller HJ, Jacobson JW, Gelmann EP, deVere White RW. p53 abnormalities in primary prostate cancer: Single-strand conformation polymorphism analysis of complementary DNA in comparison with genomic DNA. The Cooperative Prostate Network. J Natl Cancer Inst 89:66–71;1997.

    Article  PubMed  Google Scholar 

  4. Hardy GH. Mendelian properties in a mixed population. Science 28:49–50;1908.

    Google Scholar 

  5. Harris CC. p53: At the crossroads of molecular carcinogenesis and risk assessment. Science 262:1980–1981;1993.

    PubMed  Google Scholar 

  6. Henner WD, Evans AJ, Hough KM, Harris EL, Lowe BA, Beer TM. Association of codon 72 polymorphism of p53 with lower prostate cancer risk. Prostate 49:263–266;2001.

    Article  PubMed  Google Scholar 

  7. Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 351:453–456;1991.

    Article  PubMed  Google Scholar 

  8. Liu G, Miller DP, Zhou W, Thurston SW, Fan R, Xu L-L, Lynch TJ, Wain JC, Su L, Christiani DC. Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma. Cancer Res 61:8718–8722;2001.

    PubMed  Google Scholar 

  9. Makni H, Franco EL, Kaiano J, Villa LL, Labresque S, Dudley R, Storey A, Matlashewski G. p53 polymorphism in codon 72 and risk of human papillomavirus-associated cervical cancer: Effect of inter-laboratory variation. Int J Cancer 87:528–533;2000.

    Article  PubMed  Google Scholar 

  10. Malkin D, Li FP, Fraumeni JFJr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, Friend SH. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science 250:1233–1238;1990.

    PubMed  Google Scholar 

  11. Marin MC, Jost CA, Brooks LA, Irwin MS, O'Nions J, Tidy JA, James N, McGregor JM, Harwood CA, Julug IG, Vousden KH, Allday MJ, Gusterson B, Ikawa S, Hinds PW, Crook T, Kaelin WG. A common polymorphism acts as an intragenic modifier of mutant p53 behaviour. Nat Genet 25:47–54;2000.

    Article  PubMed  Google Scholar 

  12. Marx J. How p53 suppresses cell growth. Science 262:1644–1645;1993.

    PubMed  Google Scholar 

  13. Nakano Y, Naoe T, Kiyoi H, Kunishima S, Minami S, Miyawaki S, Asou N, Kuriyama K, Saito H, Ohno R. Poor clinical significance of p53 gene polymorphism in acute myeloid leukemia. Leuk Res 24:349–352;2000.

    Article  PubMed  Google Scholar 

  14. Ngan HY, Liu VW, Liu SS, Cheng DK, Ng TY, Wong LC. Homozygous arginine at codon 72 of p53 has no prognostic significance in cervical cancer. Tumor Biol 21:135–138;2000.

    Article  Google Scholar 

  15. Ohtake N, Hatori M, Yamanaka H, Nakata S, Sada M, Tsuji T. Familial prostate cancer in Japan. Int J Urol 5:138–145;1998.

    PubMed  Google Scholar 

  16. Ohtake N, Nakata S, Sato J, Koya A, Saruki K, Kurihara J, Tsuji H, Imai K, Yamanaka H, Suzuki K, Tari K. Significance of measurement of prostate specific antigen (PSA) in familial prostate cancer lines. Tohoku J Exp Med 184:21–28;1998.

    PubMed  Google Scholar 

  17. Ruijter E, van de Kaa C, Miller G, Ruiter D, Debruyne F, Schalken J. Molecular genetics and epidemiology of prostate carcinoma. Endocr Rev 20:22–45;1999.

    Article  PubMed  Google Scholar 

  18. Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature 393:229–234;1998.

    Article  PubMed  Google Scholar 

  19. Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G. Two polymorphic variations of wild-type p53 differ biochemically and biologically. Mol Cell Biol 19:1092–1100;1999.

    PubMed  Google Scholar 

  20. Tsai MH, Lin CD, Hsieh YY, Chang FC, Tsai FJ, Chen WC, Tsai CH. Prognostic significance of the proline form of p53 codon 72 polymorphism in nasopharyngeal carcinoma. Laryngoscope 112:116–119;2002.

    Article  PubMed  Google Scholar 

  21. Wang Y-C, Chen C-Y, Chen S-K, Chang Y-Y, Lin P. p53 codon 72 polymorphism in Taiwanese lung cancer patients: Association with lung cancer susceptibility and prognosis. Clin Cancer Res 5:129–134;1999.

    PubMed  Google Scholar 

  22. Wang YC, Lee HS, Chen SK, Chang YY, Chen CY. Prognostic significance of p53 codon 72 polymorphism in lung carcinomas. Eur J Cancer 35:226–230;1999.

    Article  PubMed  Google Scholar 

  23. Wu W-J, Kakehi Y, Habuchi T, Kinoshita H, Ogawa O, Terachi T, Huang C-H, Chiang C-P, Yoshida O. Allelic frequency of p53 gene codon 72 polymorphism in urological cancers. Jpn J Cancer Res 86:730–736;1995.

    PubMed  Google Scholar 

  24. Zang W, Hu G, Deisseroth A. Polymorphism at codon 72 of the p53 gene in human acute myelogeneous leukemia. Gene 117:271–275;1992.

    Article  PubMed  Google Scholar 

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Suzuki, K., Matsui, H., Ohtake, N. et al. A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese. J Biomed Sci 10, 430–435 (2003). https://doi.org/10.1007/BF02256434

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  • DOI: https://doi.org/10.1007/BF02256434

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